The DOI matches its Crossref record; 48 of the 49 references it cites were found in a registry or an index; 3 of the 35 sources its claims cite were checked for support.
Mislocalization of the Cell Polarity Protein Scribble Promotes Mammary Tumorigenesis and Is Associated with Basal Breast Cancer
Open accessPublished version of a preprint
Abstract
Scribble (SCRIB) localizes to cell–cell junctions and regulates establishment of epithelial cell polarity. Loss of expression of SCRIB functions as a tumor suppressor in Drosophila and mammals; conversely, overexpression of SCRIB promotes epithelial differentiation in mammals. Here, we report that SCRIB is frequently amplified, mRNA overexpressed, and protein is mislocalized from cell–cell junctions in human breast cancers. High levels of SCRIB mRNA are associated with poor clinical prognosis, identifying an unexpected role for SCRIB in breast cancer. We find that transgenic mice expressing a SCRIB mutant [Pro 305 to Leu (P305L)] that fails to localize to cell–cell junctions, under the control of the mouse mammary tumor virus long terminal repeat promoter, develop multifocal hyperplasia that progresses to highly pleomorphic and poorly differentiated tumors with basal characteristics. SCRIB interacts with phosphatase and tensin homolog (PTEN) and the expression of P305L, but not wild-type SCRIB, promotes an increase in PTEN levels in the cytosol. Overexpression of P305L, but not wild-type SCRIB, activates the Akt/mTOR/S6K signaling pathway. Human breast tumors overexpressing SCRIB have high levels of S6K but do not harbor mutations in PTEN or PIK3CA, identifying SCRIB amplification as a mechanism of activating PI3K signaling in tumors without mutations in PIK3CA or PTEN. Thus, we demonstrate that high levels of mislocalized SCRIB functions as a neomorph to promote mammary tumorigenesis by affecting subcellular localization of PTEN and activating an Akt/mTOR/S6kinase signaling pathway. Cancer Res; 74(11); 3180–94. ©2014 AACR.
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73 Own result · 38 Own interpretation · 27 Not checked yet · 1 Supported · 1 Partly supported · accuracy not yet measured
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In the paper
“hSCRIB protein is mislocalized from cell-cell junctions in multiple human cancers, including breast, prostate and colon (2, 3).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Introduction
What the sources say
- Partly supportedcites [2] Zhan, 2008, Deregulation of Scribble promotes mammary tumorigenesis and reveals a role for cell polarity in carcinoma, Cell sourceExperimental — accuracy not yet measured
The Results sections on human breast cancer cell lines and primary breast cancers report Scribble mislocalization away from cell-cell junctions, including in 10 of 20 DCIS samples. The passages do not establish the same finding for prostate cancer; the cited colon work appears in the References, but these passages do not establish junctional mislocalization in colon cancer. (LLM, conf=0.87)
- Partly supportedcites [3] Pearson, 2011, SCRIB expression is deregulated in human prostate cancer, and its deficiency in mice promotes prostate neoplasia, J Clin Invest sourceExperimental — accuracy not yet measured
The Introduction and Discussion state that SCRIB is mislocalized in human colorectal and breast cancers, and the Results report mislocalization in human prostate cancer. But the Results and Figure 6 description classify one prostate pattern as clustering at cell-cell junctions, so the source does not support the more specific claim that mislocalization is always away from those junctions. Page numbers are not available in our copy. (LLM, conf=0.86)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Knockdown of PTEN in normal mammary epithelial cells implanted into humanized mouse fat pads resulted in disorganized, hyperplastic lesions (44).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Discussion
What the sources say
- Supportedcites [44] Korkaya, 2009, Regulation of mammary stem/progenitor cells by PTEN/Akt/β-catenin signaling, PLoS Biol source
The Results section (Figure 2 and the accompanying text) reports that PTEN knockdown in normal mammary epithelial cells produced disorganized hyperplastic outgrowths in humanized NOD/SCID mice. The Materials and Methods section confirms that the cells were injected into humanized mouse mammary fat pads. (LLM, conf=0.95)
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In the paper
“11 of the 20 samples showed predominantly cytosolic SCRIB localization (Fig. 1Eiii), while the remaining nine showed a combination of membrane and cytosolic localization (Fig. 1Ei,ii).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > Characterization of SCRIB localization in human breast tumors
plainn = 20- Asserted: passes — The authors put it forward as true.
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In the paper
“transgenic mice expressing a SCRIB mutant (Pro 305 to Leu (P305L)) that fails to localize to cell-cell junctions, under the control of the mouse mammary tumor virus long terminal repeat promoter, develop multifocal hyperplasia”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Abstract
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- Rests on an assumption: The tumorigenic effect in hSCRIBP305L mice is attributable to SCRIB mislocalization rather than to SCRIB overexpression alone.
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In the paper
“In cells expressing SCRIBWT, addition of EGF led to three-fold increase Ser473 phosphorylation within 2.5 minutes, with a peak at 5 minutes after stimulation.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes activation of Akt
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In the paper
“In parental MCF-10A cells, an EGF stimulation-induced increase in substrate phosphorylation was detectable by 30 minutes.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes activation of Akt
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“hSCRIBP305L mice displayed higher levels of SCRIB protein in the mammary gland than control mice.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > Generation and characterization of MMTV-hSCRIBP305L mice
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In the paper
“SCRIB mRNA was upregulated, in the absence of genomic amplification, in 68 samples (9.1%).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > Genomic and gene expression changes in SCRIB associated with breast cancer
plainn = 68- Asserted: passes — The authors put it forward as true.
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In the paper
“neither SCRIBWT nor hSCRIBP305L modified EGF-stimulated JNK or p38 kinase phosphorylation (data not shown).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes activation of Akt
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“In MCF-10A cells expressing hSCRIBP305L, PRAS40 phosphorylation was both enhanced and sustained at all time points tested, as compared with control cells or those expressing SCRIBWT.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes activation of Akt
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In the paper
“one of the 14 hSCRIBP305L tumor-bearing mice revealed intravascular tumor emboli in lung tissue (Fig. 5D)”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization generates mammary tumors with high pathologic diversity
plainSingle case- Asserted: passes — The authors put it forward as true.
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In the paper
“all samples analyzed (6/6) expressed decreased levels of these markers compared with NDL tumors (Fig. 5G).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes mammary tumors with basal characteristics
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“all six hSCRIBP305L tumors analyzed expressed dramatically enhanced levels (10- to 60-fold increase) of at least two of these basal markers.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes mammary tumors with basal characteristics
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“In contrast, in MCF10A cells, and those expressing SCRIBWT, EGF stimulation did not significantly increase p70S6K phosphorylation up to 45 minutes after stimulation.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes activation of Akt
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“MCF-10A cells expressing hSCRIBP305L displayed a marked increase in Akt308 phosphorylation as compared with either control or SCRIBWT cells (Fig. 6C).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes activation of Akt
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“the expression of P305L, but not wild-type SCRIB, promotes an increase in PTEN levels in the cytosol.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Abstract
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In the paper
“High levels of SCRIB mRNA are associated with poor clinical prognosis”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Abstract
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In the paper
“Penetrance of the tumor phenotype reached as high as 55% by two years of age in P305L2”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > hSCRIBP305L mice develop spontaneous mammary tumors
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In the paper
“In parental MCF-10A cells, Akt is phosphorylated at Ser473 within 5 minutes of EGF stimulation (Fig. 6C).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes activation of Akt
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The kinetics and amplitude of EGF-stimulated ERK phosphorylation was similar in cells expressing either SCRIBWT or hSCRIBP305L.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes activation of Akt
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“In adult virgin mammary glands of FVB mice, SCRIB co-localizes with E-cad to the basolateral surface of luminal epithelial cells (Fig. 2C,D, left panels).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > Generation and characterization of MMTV-hSCRIBP305L mice
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In the paper
“In hSCRIBP305L mice, SCRIB expression in the mammary gland was primarily expressed in E-cad positive luminal epithelial cells (Fig. 2C,D, right panels).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > Generation and characterization of MMTV-hSCRIBP305L mice
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“In MCF-10A cells expressing SCRIBWT, addition of EGF led to higher levels of Akt308 phosphorylation (Fig. 6C).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes activation of Akt
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In the paper
“However, cells expressing hSCRIBP305L showed a greater increase in signal compared to those observed in parental or SCRIBWT expressing cells (Supp. Fig 4A)”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes activation of Akt
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In the paper
“SCRIB interacts with PTEN”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Quantitative analysis of hSCRIBP305L mice through 50 weeks of age demonstrated a significant impairment in tertiary side branching as compared with control mice (Fig. 3B).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > hSCRIBP305L mice display mammary morphogenesis defects
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In the paper
“MCF-10A cells expressing hSCRIBP305L displayed enhanced phosphorylation of p70S6K and S6 45 minutes after EGF stimulation, as compared with MCF-10A cells or MCF-10A cells expressing SCRIBWT (Fig. 6F).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes activation of Akt
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In the paper
“Virgin hSCRIBP305L mice, but not FVB control mice, developed regions of hyperplastic growth, as determined by whole mount carmine alum-stained mammary glands (Fig. 4A) and H&E-stained sections (Fig. 4B).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > hSCRIBP305L mice develop multifocal hyperplasia
plainn = 10- Asserted: passes — The authors put it forward as true.
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In the paper
“In MCF-10A cells grown in the absence of EGF, phosphorylation of Akt at Thr308 was undetectable (Fig. 6C).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes activation of Akt
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In the paper
“Here we find that SCRIB was significantly upregulated in Basal-like 1 (BL1) and Mesenchymal (M), as compared with Basal-like 2 (BL2), Immunomodulatory (IM), Mesenchymal stem-like (MSL) and Luminal androgen receptor (LAR) (Fig. 1C, Supp. Figs. 1D,E)”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > Genomic and gene expression changes in SCRIB associated with breast cancer
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In the paper
“that progresses to highly pleomorphic and poorly differentiated tumors with basal characteristics”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: The tumorigenic effect in hSCRIBP305L mice is attributable to SCRIB mislocalization rather than to SCRIB overexpression alone.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“MCF-10A cells expressing hSCRIBP305L displayed phosphorylation of p70S6K as early as 15 minutes following EGF stimulation, which was maintained through 45 minutes (Fig 6E).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes activation of Akt
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In the paper
“the hyperplasia phenotype was highly penetrant and observed in 8/10 transgenic mice older than one year of age (Fig. 4C).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > hSCRIBP305L mice develop multifocal hyperplasia
plainn = 10- Asserted: passes — The authors put it forward as true.
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In the paper
“Within one and a half years of age, virgin hSCRIBP305L mice from two distinct lines developed focal mammary tumors (Fig. 5A).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > hSCRIBP305L mice develop spontaneous mammary tumors
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In the paper
“However, within the luminal epithelial cells of hSCRIBP305L mice, SCRIB is localized throughout the cytosol (Fig. 2D).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > Generation and characterization of MMTV-hSCRIBP305L mice
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In the paper
“Expression of hSCRIBP305L enhanced EGF-induced phosphorylation of TSC2, as compared with MCF-10A cells and those expressing SCRIBWT (Fig. 6D).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes activation of Akt
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“we observed that SCRIB expression was significantly higher in the basal and luminal B tumors, as compared with luminal A, Her2 and normal-like tumors.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > Genomic and gene expression changes in SCRIB associated with breast cancer
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“high SCRIB expression predicts for worse overall survival (HR = 1.61, p < 0.0007; Fig 1D).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > Genomic and gene expression changes in SCRIB associated with breast cancer
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“hSCRIBP305L tumors displayed enhanced phosphorylation of S6, as compared with NDL controls.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > hSCRIBP305L mammary tumors and human breast cancers with amplified SCRIB show activation of S6 kinase but no correlation with mutations in PTEN or PIK3CA
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“By contrast, SCRIB amplification did not correlate with HER2 amplification in human breast cancer (p=0.06, n=760).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > hSCRIBP305L mammary tumors and human breast cancers with amplified SCRIB show activation of S6 kinase but no correlation with mutations in PTEN or PIK3CA
plainn = 760- Asserted: passes — The authors put it forward as true.
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In the paper
“Western blot analysis of mammary glands isolated from FVB and hSCRIBP305L mice at 30 weeks (Fig. 7H), and hyperplastic glands at 75 weeks (Fig. 7I) showed higher levels of phospho-S6 in hSCRIBP305L glands.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > hSCRIBP305L mammary tumors and human breast cancers with amplified SCRIB show activation of S6 kinase but no correlation with mutations in PTEN or PIK3CA
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Whereas no PTEN was pulled down in the control IP (IgG), endogenous SCRIB was able to pull down endogenous PTEN.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB interacts with PTEN in a PDZ domain-dependent manner
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, IHC analysis showed enhanced phospho-Akt308 in hSCRIBP305L tumors (Fig. 7K).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > hSCRIBP305L mammary tumors and human breast cancers with amplified SCRIB show activation of S6 kinase but no correlation with mutations in PTEN or PIK3CA
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Similar to our findings with mouse tumors induced by expressing mislocalized SCRIB, tumors with SCRIB amplification had higher levels of phosphorylated S6 as compared to non-amplified tumors (Fig. 7L).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > hSCRIBP305L mammary tumors and human breast cancers with amplified SCRIB show activation of S6 kinase but no correlation with mutations in PTEN or PIK3CA
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our sequencing efforts and those reported by TCGA do not show evidence of frequent mutations in SCRIB suggesting that changes in Scribble localization must involve alternate mechanisms.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Discussion
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“In the presence of rapamycin, mTORC1-mediated phosphorylation of p70S6K and S6 proteins was inhibited (Fig 6F).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes activation of Akt
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Whereas GFP-PTEN was able to bind T7-WTSCRIB, or PDZ mutants P2, P3 and P4, mutation of the first PDZ domain of SCRIB significantly reduced the SCRIB/PTEN interaction (Fig. 7D,E).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB interacts with PTEN in a PDZ domain-dependent manner
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Consistently, we find that transgenic mice co-expressing hSCRIBP305L and NEU/HER2 under the control of MMTV promoter did not show any change in latency of tumor onset (Supp. Fig. 4C)”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > hSCRIBP305L mammary tumors and human breast cancers with amplified SCRIB show activation of S6 kinase but no correlation with mutations in PTEN or PIK3CA
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“SCRIB amplification correlated with alterations in TP53, BRCA1, BRCA2, FGFR1, EGFR, MAP3K1 and ZNF217, demonstrating a correlation between SCRIB amplification and genes frequently altered in aggressive forms of breast cancer.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > hSCRIBP305L mammary tumors and human breast cancers with amplified SCRIB show activation of S6 kinase but no correlation with mutations in PTEN or PIK3CA
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Consistent with this observation, there was a strong correlation between SCRIB and MYC co-amplification in human breast cancer (p=0, n=760) (Fig. 7M).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > hSCRIBP305L mammary tumors and human breast cancers with amplified SCRIB show activation of S6 kinase but no correlation with mutations in PTEN or PIK3CA
boostedcorrelationaln = 760- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At the eight-week time point, no change was seen in the intensity of pS6 staining between FVB and hSCRIBP305L mice.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > hSCRIBP305L mammary tumors and human breast cancers with amplified SCRIB show activation of S6 kinase but no correlation with mutations in PTEN or PIK3CA
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“MCF-10A cells expressing hSCRIBP305L had a more than three-fold increase in cytosolic PTEN than the parental or WTSCRIB expressing cells (Fig. 7F, left panels).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB interacts with PTEN in a PDZ domain-dependent manner
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“As expected, mTORC2 mediated phosphorylation of Akt at 473 was not affected in rapamycin treated cells (Fig 6G).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes activation of Akt
plain- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, SCRIB mislocalization specifically induces activation of Akt/mTOR pathway that leads to activation of downstream targets in mammary epithelial cells.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes activation of Akt
plaindirect- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: Akt phosphorylation at Thr308 and Ser473 is associated with increased Akt kinase activity.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“demonstrating that overexpression of mislocalized SCRIB can initiate tumorigenesis in the mouse mammary gland.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > hSCRIBP305L mice develop spontaneous mammary tumors
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: The tumorigenic effect in hSCRIBP305L mice is attributable to SCRIB mislocalization rather than to SCRIB overexpression alone.
- Rests on an assumption: The hSCRIBP305L transgene is the cause of the mammary tumors, not spontaneous or insertional mutagenesis.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These observations demonstrated that the SCRIB gene is frequently amplified or overexpressed and not lost or downregulated in breast tumors.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > Genomic and gene expression changes in SCRIB associated with breast cancer
boostedcorrelationaln = 748- Asserted: passes — The authors put it forward as true.
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In the paper
“In prostate cancer, hSCRIB mislocalization is correlated with poor patient survival (3).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Introduction
What the sources say
- Not checked yetcites [3] Pearson, 2011, SCRIB expression is deregulated in human prostate cancer, and its deficiency in mice promotes prostate neoplasia, J Clin Invest source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“our results suggest that expression of mislocalized SCRIB results in accumulation of luminal progenitor cells in the mammary gland.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > hSCRIBP305L mice display mammary morphogenesis defects
hedgeddirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results demonstrate that overexpression of mislocalized SCRIB disrupts mammary gland morphogenesis.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > hSCRIBP305L mice display mammary morphogenesis defects
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In epithelial cells, SCRIB localizes to cell-cell junctions”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Introduction
What the sources say
- Not checked yetcites [11] Zeitler, 2004, Domains controlling cell polarity and proliferation in the Drosophila tumor suppressor Scribble, J Cell Biol source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“These observations demonstrate that basolateral membrane localization is required for normal SCRIB function in both Drosophila and mammals.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Introduction
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“mislocalization of SCRIB phenocopies a complete null phenotype in Drosophila (11)”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Introduction
What the sources say
- Not checked yetcites [11] Zeitler, 2004, Domains controlling cell polarity and proliferation in the Drosophila tumor suppressor Scribble, J Cell Biol source
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“identifying SCRIB amplification as a mechanism of activating PI3K signaling in tumors without mutations in PIK3CA or PTEN.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“suggesting that expression of hSCRIBP305L activates Akt in MCF-10A cells.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes activation of Akt
hedgeddirect- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: Akt phosphorylation at Thr308 and Ser473 is associated with increased Akt kinase activity.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is likely that SCRIB localization is dysregulated by multiple mechanisms in cancer cell lines and human tumors.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > Characterization of SCRIB localization in human breast tumors
hedgedconditionaln = 20- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We report that mislocalization of SCRIB results in acquisition of a new function (neomorph), it mislocalizes PTEN and activates a mTORC1/Akt/S6K pathway and thus results in a gain of function.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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- Rests on an assumption: Akt phosphorylation at Thr308 and Ser473 is associated with increased Akt kinase activity.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these observations begin to explain why high levels of SCRIB are frequently selected-for in breast cancers.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: SCRIB mislocalization is highly prevalent in human tumors.
In the paper
“Despite high pathway activity, basal-like cancers rarely display PIK3CA (PI3K catalytic domain) mutations (48).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Discussion
What the sources say
- Not checked yetcites [48] Stemke-Hale, 2008, An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer, Cancer Res source
plain- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Taken together our observations demonstrate that amplification or overexpression of SCRIB is associated with aggressive subtypes of human breast cancer”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > hSCRIBP305L mammary tumors and human breast cancers with amplified SCRIB show activation of S6 kinase but no correlation with mutations in PTEN or PIK3CA
boostedcorrelationaln = 760- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We report that mislocalization of SCRIB results in acquisition of a new function (neomorph), it mislocalizes PTEN and activates a mTORC1/Akt/S6K pathway and thus results in a gain of function.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The above results, taken together, identify mTOR and Akt signaling as downstream effectors of expression of hSCRIBP305L.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes activation of Akt
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Akt phosphorylation at Thr308 and Ser473 is associated with increased Akt kinase activity.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We report that mislocalization of SCRIB results in acquisition of a new function (neomorph), it mislocalizes PTEN and activates a mTORC1/Akt/S6K pathway and thus results in a gain of function.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Furthermore, a mouse model in which direct activation of PI3K was accomplished by recruitment of p110α to the membrane resulted in alveolar hyperplasia and low penetrance tumorigenesis (45).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Discussion
What the sources say
- Not checked yetcites [45] Renner, 2008, Activation of phosphatidylinositol 3-kinase by membrane localization of p110α predisposes mammary glands to neoplastic transformation, Cancer Res source
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Herein, we identify an unexpected role for the polarity protein Scribble in the pathogenesis of cancer.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Discussion
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Phosphorylation of serine residues in the carboxy terminal domain of SCRIB induces mislocalization to the cytosol (41).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Discussion
What the sources say
- Not checked yetcites [41] Metodieva, 2013, CD74-dependent deregulation of the tumor suppressor Scribble in human epithelial and breast cancer cells, Neoplasia source
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, our results are consistent with a model in which aberrant Akt activation within the mouse mammary gland results in basal-like tumors.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Discussion
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Akt phosphorylation at Thr308 and Ser473 is associated with increased Akt kinase activity.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“demonstrating a correlation between SCRIB amplification and genes frequently altered in aggressive forms of breast cancer.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > hSCRIBP305L mammary tumors and human breast cancers with amplified SCRIB show activation of S6 kinase but no correlation with mutations in PTEN or PIK3CA
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“We have previously shown that expression of hSCRIBP305L cooperates with Myc during transformation of mammary epithelial cells (2).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > hSCRIBP305L mammary tumors and human breast cancers with amplified SCRIB show activation of S6 kinase but no correlation with mutations in PTEN or PIK3CA
What the sources say
- Not checked yetcites [2] Zhan, 2008, Deregulation of Scribble promotes mammary tumorigenesis and reveals a role for cell polarity in carcinoma, Cell source
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“T7-SCRIB was able to pull down WT-PTEN, but significantly less PTEN-399, demonstrating that the C-terminal PDZ binding site of PTEN is critical for the SCRIB/PTEN interaction.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB interacts with PTEN in a PDZ domain-dependent manner
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We report that mislocalization of SCRIB results in acquisition of a new function (neomorph), it mislocalizes PTEN and activates a mTORC1/Akt/S6K pathway and thus results in a gain of function.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results suggest that PTEN localization modulates EGF-induced activation of Akt.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB interacts with PTEN in a PDZ domain-dependent manner
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Our results showing that SCRIB mislocalization enhances Akt signaling and results in mammary morphogenesis defects are consistent with a mouse model of Akt pathway activation (43).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Discussion
What the sources say
- Not checked yetcites [43] Schwertfeger, 2001, Mammary gland involution is delayed by activated Akt in transgenic mice, Mol Endocrinol source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Akt phosphorylation at Thr308 and Ser473 is associated with increased Akt kinase activity.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We demonstrate that overexpression of a mislocalized form of SCRIB functions as a neomorph by interacting with another tumor suppressor, PTEN, and activating an mTORC1/Akt/S6K signaling pathway in culture and in vivo.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Discussion
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Akt phosphorylation at Thr308 and Ser473 is associated with increased Akt kinase activity.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Taken together, our results suggest that SCRIB and PTEN are present in a protein complex requiring the PDZ-binding motif of PTEN and the first PDZ domain of SCRIB.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB interacts with PTEN in a PDZ domain-dependent manner
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“demonstrating lack of cooperation between hSCRIBP305L and HER2 during mouse mammary tumorigenesis.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > hSCRIBP305L mammary tumors and human breast cancers with amplified SCRIB show activation of S6 kinase but no correlation with mutations in PTEN or PIK3CA
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Furthermore, alterations in SCRIB binding partners, including E-cadherin, may disrupt SCRIB membrane localization (42).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Discussion
What the sources say
- Not checked yetcites [42] Navarro, 2005, Junctional recruitment of mammalian Scribble relies on E-cadherin engagement, Oncogene source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that changes in Scribble localization must involve alternate mechanisms.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Discussion
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, multiple distinct mechanisms may account for the high prevalence of SCRIB mislocalization observed human tumors.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: SCRIB mislocalization is highly prevalent in human tumors.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that SCRIB amplification is mutually exclusive with alternate mechanisms of activating the PI3K signaling pathway (Fig. 7M).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > hSCRIBP305L mammary tumors and human breast cancers with amplified SCRIB show activation of S6 kinase but no correlation with mutations in PTEN or PIK3CA
hedgedcorrelationaln = 760- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 43
- Probably not a substantial claim. 12
- The quote only partly states this claim. 1
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“While the cancer cell lines all showed mislocalized SCRIB, no mutations within the Pro 305-containing LRR domain were found (data not shown).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > Characterization of SCRIB localization in human breast tumors
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The tumors were broadly classified as adenocarcinomas (29%), spindle cell tumors (14%), adenosquamous carcinoma (21%), and cystic squamous cell carcinoma (14%), while the remainder did not fall into simple classification (21%) (Fig. 5C).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization generates mammary tumors with high pathologic diversity
plainn = 14- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“MCF-10A cells expressing hSCRIBP305L displayed a nine fold increase of Ser473 phosphorylation at 2.5 minutes that was maintained through 5 minutes and decreased by 15 minutes”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes activation of Akt
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“EGF-stimulation of MCF-10A cells promoted ERK phosphorylation within 2.5 minutes, which was maintained through 15 minutes (Fig. 6C).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes activation of Akt
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Human breast tumors overexpressing SCRIB have high levels of S6K but do not harbor mutations in PTEN or PIK3CA”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overexpression of P305L, but not wild type SCRIB, activates the Akt/mTOR/S6K signaling pathway.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overexpressed SCRIBWT localizes to the cell membrane and is concentrated at cell-cell junctions, whereas hSCRIBP305L is predominantly localized to the cytosol (Fig. 6B).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes activation of Akt
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Consistently, MCF-10A cells expressing hSCRIBP305L displayed enhanced phosphorylation of S6, as compared with parental MCF-10A cells or MCF-10A cells expressing SCRIBWT (Fig. 6E).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes activation of Akt
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In MCF-10A cells, EGF stimulation induced PRAS40 phosphorylation within 2.5 minutes, returning to near basal levels by 30 minutes (Fig. 6D).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes activation of Akt
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We observed both inter-tumor and intra-tumor heterogeneity for histological characteristics (Fig. 5B, insets).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization generates mammary tumors with high pathologic diversity
plainn = 14- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“hSCRIBP305L tumors expressed lower levels of E-cadherin and high levels of Vimentin and CK14.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes mammary tumors with basal characteristics
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Addition of EGF to the cells led to an increase in Akt308 phosphorylation within 2.5 minutes, reduced after 5 minutes and returned to basal levels by 15 minutes.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes activation of Akt
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This population accounted for 17.1% of cells in hSCRIBP305L mice, a 57% increase over FVB controls.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > hSCRIBP305L mice display mammary morphogenesis defects
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast, hyperplastic hSCRIBP305L mammary glands showed increased levels of CK18-positive and double positive cells, with a decrease in the percentage of CK14-positive cells (Fig. 4D,E).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > hSCRIBP305L mice develop multifocal hyperplasia
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“SCRIB is frequently amplified, mRNA over-expressed and protein is mislocalized from cell-cell junctions in human breast cancers.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Among the 748 breast cancer samples analyzed, SCRIB was amplified in 116 tumors (15.6%), homozygous deleted in two (0.3%) and contained a somatic frame shift mutation in one (Fig. 1A).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > Genomic and gene expression changes in SCRIB associated with breast cancer
plainn = 748- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In MCF-10A cells expressing SCRIBWT, EGF induced PRAS40 phosphorylation with similar kinetics and intensity but greater at 30 minutes after EGF-stimulation.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes activation of Akt
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, ductal structures from 20-week old hSCRIBP305L mice displayed markedly higher pS6 staining than controls, and maintained this enhanced signal through 50 weeks.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > hSCRIBP305L mammary tumors and human breast cancers with amplified SCRIB show activation of S6 kinase but no correlation with mutations in PTEN or PIK3CA
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Interestingly, there was no correlation between amplification of SCRIB and mutations in PTEN (P=0.2, n=760) and PIK3CA (p=0.3, n=482), regulators of the PI3K signaling pathway,”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > hSCRIBP305L mammary tumors and human breast cancers with amplified SCRIB show activation of S6 kinase but no correlation with mutations in PTEN or PIK3CA
plainn = 760- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“T7-SCRIB was able to pull down WT-PTEN, but significantly less PTEN-399, demonstrating that the C-terminal PDZ binding site of PTEN is critical for the SCRIB/PTEN interaction.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB interacts with PTEN in a PDZ domain-dependent manner
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Expression of WT-PTEN, but not PTEN-399, attenuated EGF-induced phosphorylation of Akt (Fig. 7G).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB interacts with PTEN in a PDZ domain-dependent manner
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Importantly, both SCRIBWT and hSCRIBP305L were able to pull down PTEN.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB interacts with PTEN in a PDZ domain-dependent manner
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Akt directly phosphorylates PRAS40 at Thr246, relieving the PRAS40 inhibitory effect on the mTOR1 complex (mTORC1) (30).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes activation of Akt
What the sources say
- Not checked yetcites [30] Sancak, 2007, PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase, Mol Cell source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that the tumor cells are not benign and have the capacity to extravasate from the primary site.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization generates mammary tumors with high pathologic diversity
hedgedSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“overexpression of SCRIB in mammary epithelial cells promotes epithelial differentiation by suppressing expression of epithelial mesenchymal transition regulators in a Ras/MAPK dependent manner (4).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Introduction
What the sources say
- Not checked yetcites [4] Elsum, 2013, Scribble regulates an EMT polarity pathway through modulation of MAPK-ERK signaling to mediate junction formation, J Cell Sci
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Loss of SCRIB that results in uncontrolled proliferation and tissue growth identifying it as tumor suppressor (1).”
- Also stated in: § Introduction · plain
“In mammals, loss of SCRIB induces dysplastic growth in vivo (2, 3) identifying loss of expression as a tumor suppressive mechanism.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Introduction
What the sources say
- Not checked yetcites [1] Bilder, 2000, Localization of apical epithelial determinants by the basolateral PDZ protein Scribble, Nature source
- Not checked yetcites [2] Zhan, 2008, Deregulation of Scribble promotes mammary tumorigenesis and reveals a role for cell polarity in carcinoma, Cell source
- Not checked yetcites [3] Pearson, 2011, SCRIB expression is deregulated in human prostate cancer, and its deficiency in mice promotes prostate neoplasia, J Clin Invest source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Introduction · plain
In the paper
“mTOR phosphorylates p70S6 kinase (p70S6K) at several residues, resulting in increased kinase activity (31).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes activation of Akt
What the sources say
- Not checked yetcites [31] Pullen, 1998, Phosphorylation and activation of p70s6k by PDK1, Science source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that Akt kinase is activated early in both SCRIBWT and hSCRIBP305L expressing cells but sustained longer in cells expressing hSCRIBP305L.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes activation of Akt
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Akt phosphorylation at Thr308 and Ser473 is associated with increased Akt kinase activity.
In the paper
“Active p70S6K phosphorylates the ribosomal protein S6, enhancing translation of mRNA transcripts involved in cell cycle progression (32).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes activation of Akt
What the sources say
- Not checked yetcites [32] Jefferies, 1997, Rapamycin suppresses 5′TOP mRNA translation through inhibition of p70s6k, EMBO J source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Akt directly phosphorylates TSC2 at Thr1462, resulting in activation of mTORC1 (29).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes activation of Akt
What the sources say
- Not checked yetcites [29] Manning, 2002, Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway, Mol Cell source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These observations demonstrate that SCRIB overexpression is associated with the aggressive forms of breast cancers and with poor clinical prognosis.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > Genomic and gene expression changes in SCRIB associated with breast cancer
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We show that expression of hSCRIBP305L induces mammary tumors, providing direct evidence that SCRIB mislocalization can have a causal role during tumorigenesis.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Introduction
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The tumorigenic effect in hSCRIBP305L mice is attributable to SCRIB mislocalization rather than to SCRIB overexpression alone.
- Rests on an assumption: The hSCRIBP305L transgene is the cause of the mammary tumors, not spontaneous or insertional mutagenesis.
In the paper
“A specific point mutation within LRR13 (Prol 305 to Leu, P305L) of the human SCRIB protein (hSCRIB) has also been shown to abrogate membrane localization (13), disrupting recruitment of βPIX, and exocytosis.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Introduction
What the sources say
- Not checked yetcites [13] Audebert, 2004, Mammalian Scribble forms a tight complex with the βPIX exchange factor, Curr Biol source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Taken together, our data provide evidence that SCRIB mislocalization induces histologically diverse mammary tumors with basal characteristics.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes mammary tumors with basal characteristics
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, we demonstrate that high levels of mislocalized SCRIB functions as a neomorph to promote mammary tumorigenesis by affecting subcellular localization of PTEN and activating an Akt/mTOR/S6kinase signaling pathway.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Abstract
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The tumorigenic effect in hSCRIBP305L mice is attributable to SCRIB mislocalization rather than to SCRIB overexpression alone.
In the paper
“overexpression of wild-type hSCRIB in MCF-10A mammary epithelial cells grown in 3D had no impact on morphogenesis, whereas expression of hSCRIBP305L displayed defective morphogenesis (2).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Introduction
What the sources say
- Not checked yetcites [2] Zhan, 2008, Deregulation of Scribble promotes mammary tumorigenesis and reveals a role for cell polarity in carcinoma, Cell source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Akt is also phosphorylated within the carboxyl-terminal hydrophobic motif at Ser473 by the serine/threonine kinase mammalian target of rapamycin complex 2 (mTORC2), within a rapamycin-insensitive protein complex (27).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB mislocalization promotes activation of Akt
What the sources say
- Not checked yetcites [27] Sarbassov, 2005, Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex, Science source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“In addition, Scribble is required for directional migration, promotes epithelial identity and suppresses epithelial to mesenchymal transition in mammary and corneal epithelial cells (4, 5, 39).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Discussion
What the sources say
- Not checked yetcites [4] Elsum, 2013, Scribble regulates an EMT polarity pathway through modulation of MAPK-ERK signaling to mediate junction formation, J Cell Sci
- Not checked yetcites [5] Yamben, 2013, Scrib is required for epithelial cell identity and prevents epithelial to mesenchymal transition in the mouse, Dev Biol source
- Not checked yetcites [39] Dow, 2007, The tumour-suppressor Scribble dictates cell polarity during directed epithelial migration: regulation of Rho GTPase recruitment to the leading edge, Oncogene source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Others and we have previously reported that downregulation (or loss) of SCRIB expression functions as a tumor suppressor by inhibiting cell death or inducing proliferation (2, 3).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Discussion
What the sources say
- Not checked yetcites [2] Zhan, 2008, Deregulation of Scribble promotes mammary tumorigenesis and reveals a role for cell polarity in carcinoma, Cell source
- Not checked yetcites [3] Pearson, 2011, SCRIB expression is deregulated in human prostate cancer, and its deficiency in mice promotes prostate neoplasia, J Clin Invest source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As we report here, large-scale cancer genome analysis identifies SCRIB gene amplification and overexpression as a frequent and clinically relevant event in breast cancer and not deletion or decrease in gene expression, raising new questions on how SCRIB may regulate the biology of cancer cells.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A recent analysis, combining mutation, mRNA expression and protein levels, determined that the PI3K/Akt pathway was elevated in basal-like cancers as compared with luminal or HER2+ (47).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Discussion
What the sources say
- Not checked yetcites [47] Cancer Genome Atlas Network, 2012, Comprehensive molecular portraits of human breast tumours, Nature source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“These outgrowths displayed increased basal markers (smooth muscle actin, CK5, CK6) and decreased luminal markers (estrogen receptor, CK18), similar to our findings with mislocalization of SCRIB.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Discussion
What the sources say
- Not checked yetcites [44] Korkaya, 2009, Regulation of mammary stem/progenitor cells by PTEN/Akt/β-catenin signaling, PLoS Biol source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In support of this hypothesis, proper vesicle trafficking is critical for maintenance of epithelial polarity (40).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Discussion
What the sources say
- Not checked yetcites [40] Mellman, 2008, Coordinated protein sorting, targeting and distribution in polarized cells, Nat Rev Mol Cell Biol source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is likely that the gain of function associated with hSCRIBP305L drives tumorigenesis and contributes to the invasive behavior observed in mammary tumors.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Mice in which PTEN was deleted within the mammary epithelium developed pathologically heterogeneous tumors with high expression of basal markers (46).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Discussion
What the sources say
- Not checked yetcites [46] Li, 2002, Conditional loss of PTEN leads to precocious development and neoplasia in the mammary gland, Development source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and that mice overexpressing SCRIB activate a PI3K/S6K pathway and induce formation of mammary tumors with the basal subtype.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > hSCRIBP305L mammary tumors and human breast cancers with amplified SCRIB show activation of S6 kinase but no correlation with mutations in PTEN or PIK3CA
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Akt phosphorylation at Thr308 and Ser473 is associated with increased Akt kinase activity.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We demonstrate that overexpression of a mislocalized form of SCRIB functions as a neomorph by interacting with another tumor suppressor, PTEN, and activating an mTORC1/Akt/S6K signaling pathway in culture and in vivo.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Discussion
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these observations suggest a working model that SCRIB normally promotes epithelial differentiation and loss of expression results in mesenchymal transition and tumorigenesis.”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Discussion
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Furthermore, knockdown of PTEN in mammary epithelial cells grown in 3D culture results in hyperproliferation and disrupted acinar organization (37).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB interacts with PTEN in a PDZ domain-dependent manner
What the sources say
- Not checked yetcites [37] Stiles, 2004, PTENless means more, Dev Biol source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Loss of PTEN enhances PIP3-mediated signaling, including phosphorylation and activation of Akt (36).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB interacts with PTEN in a PDZ domain-dependent manner
What the sources say
- Not checked yetcites [36] Wu, 1998, The PTEN/MMAC1 tumor suppressor phosphatase functions as a negative regulator of the phosphoinositide 3-kinase/Akt pathway, Proc Natl Acad Sci U S A source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“PTEN is a phosphatase that dephosphorylates phosphatidylinositol (3,4,5)-trisphosphate (PIP3), a second messenger generated by phosphoinositide 3-kinase (PI3K) (35).”
§ Mislocalization of the cell polarity protein Scribble promotes mammary tumorigenesis and is associated with basal breast cancer > Results > SCRIB interacts with PTEN in a PDZ domain-dependent manner
What the sources say
- Not checked yetcites [35] Maehama, 1998, The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate, J Biol Chem source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
The paper relies on this without support.
The tumorigenic effect in hSCRIBP305L mice is attributable to SCRIB mislocalization rather than to SCRIB overexpression alone.
“To investigate the effect of expressing Scribble that does not localize to cell-cell junctions, we generated a transgenic mouse expressing hSCRIBP305L”
The paper relies on this without support.
The hSCRIBP305L transgene is the cause of the mammary tumors, not spontaneous or insertional mutagenesis.
“Virgin hSCRIBP305L mice, but not FVB control mice, developed regions of hyperplastic growth”
The paper relies on this without support.
Akt phosphorylation at Thr308 and Ser473 is associated with increased Akt kinase activity.
“Phosphorylation of Akt at 308 and 473 is associated with an increase in its kinase activity.”
The paper relies on this without support.
SCRIB mislocalization is highly prevalent in human tumors.
“Therefore, multiple distinct mechanisms may account for the high prevalence of SCRIB mislocalization observed human tumors.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“The tumor-suppressive activity of Scrib correlates with its membrane localization.”
From Membrane recruitment of the polarity protein Scribble by the cell adhesion receptor TMIGD1 (2023) · cites this paper as [18]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Importantly, ectopic expression of Scrib/P305L in cell lines disrupts cell polarity, suppresses c-myc-induced apoptosis, enhances Akt signaling, and fails to suppress Ras-MAPK-induced EMT18,47,56,68.”
From Membrane recruitment of the polarity protein Scribble by the cell adhesion receptor TMIGD1 (2023) · cites this paper as [18]
The cited source says what the claim attributes to it.
In the citing paper
“Importantly, ectopic expression of Scrib/P305L in cell lines disrupts cell polarity, suppresses c-myc-induced apoptosis, enhances Akt signaling, and fails to suppress Ras-MAPK-induced EMT18,47,56,68.”
From Membrane recruitment of the polarity protein Scribble by the cell adhesion receptor TMIGD1 (2023) · cites this paper as [18]
The cited source says what the claim attributes to it.
In the citing paper
“Also, transgenic mice expressing Scrib/P305L in the mammary gland display hyperplastic growth in the mammary gland and develop mammary tumors18.”
From Membrane recruitment of the polarity protein Scribble by the cell adhesion receptor TMIGD1 (2023) · cites this paper as [18]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Importantly, ectopic expression of Scrib/P305L in cell lines disrupts cell polarity, suppresses c-myc-induced apoptosis, enhances Akt signaling, and fails to suppress Ras-MAPK-induced EMT18,47,56,68.”
From Membrane recruitment of the polarity protein Scribble by the cell adhesion receptor TMIGD1 (2023) · cites this paper as [18]
Experimental — accuracy not yet measured
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Importantly, ectopic expression of Scrib/P305L in cell lines disrupts cell polarity, suppresses c-myc-induced apoptosis, enhances Akt signaling, and fails to suppress Ras-MAPK-induced EMT18,47,56,68.”
From Membrane recruitment of the polarity protein Scribble by the cell adhesion receptor TMIGD1 (2023) · cites this paper as [18]
Experimental — accuracy not yet measuredIn the citing paper
“Junctional localization of Scribble may play a tumor suppressor role, because in several models altered Scribble localization is associated with tumor initiation or progression (Feigin et al., 2014; Wan et al., 2018).”
From Scribble: A master scaffold in polarity, adhesion, synaptogenesis, and proliferation (2019) · cites this paper as Feigin et al., 2014
In the citing paper
“Similarly, conditional mammary gland knockout did not disrupt initial gland architecture but at maturity led to ductal hyperplasia (Godde et al., 2014), a phenotype mimicked by an LRR point mutant (Feigin et al., 2014).”
From Scribble: A master scaffold in polarity, adhesion, synaptogenesis, and proliferation (2019) · cites this paper as Feigin et al., 2014
Citations
Cites
Cerami, E., Gao, J., Dogrusoz, U., Gross, B. E., Sumer, S. O., Aksoy, B. A., Jacobsen, A., Byrne, C. J., Heuer, M. L., Larsson, E., et al. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0095 · Cited by 17,455
Comprehensive molecular portraits of human breast tumours
The Cancer Genome Atlas Network (2012) · Nature · doi:10.1038/nature11412 · Cited by 12,129
Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex
Sarbassov, D. D., Guertin, D. A., Ali, S. M., & Sabatini, D. M. (2005) · Science · doi:10.1126/science.1106148 · Cited by 6,216
Lehmann, B. D., Bauer, J. A., Chen, X., Sanders, M. E., Chakravarthy, A. B., Shyr, Y., & Pietenpol, J. A. (2011) · Journal of Clinical Investigation · doi:10.1172/jci45014 · Cited by 5,592
Self-citationLi, J., Yen, C., Liaw, D., Podsypanina, K., Bose, S., Wang, S. I., Puc, J., Miliaresis, C., Rodgers, L., McCombie, R., et al. (1997) · Science · doi:10.1126/science.275.5308.1943 · Cited by 4,785
Györffy, B., Lanczky, A., Eklund, A. C., Denkert, C., Budczies, J., Li, Q., & Szallasi, Z. (2010) · Breast Cancer Research and Treatment · doi:10.1007/s10549-009-0674-9 · Cited by 4,169
Maehama, T., & Dixon, J. E. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.22.13375 · Cited by 3,104
Alessi, D. R., James, S. R., Downes, C. P., Holmes, A. B., Gaffney, P. R. J., Reese, C. B., & Cohen, P. (1997) · Current Biology · doi:10.1016/s0960-9822(06)00122-9 · Cited by 2,874
Steck, P. A., Pershouse, M. A., Jasser, S. A., Yung, W. K. A., Lin, H., Ligon, A. H., Langford, L. A., Baumgard, M. L., Hattier, T., Davis, T., et al. (1997) · Nature Genetics · doi:10.1038/ng0497-356 · Cited by 2,742
Debnath, J., Muthuswamy, S. K., & Brugge, J. S. (2003) · Methods · doi:10.1016/s1046-2023(03)00032-x · Cited by 2,001
Self-citation
Cited by
Sorted by citations
The role of lipids in cancer progression and metastasis
Martín‐Pérez, M., Urdiroz-Urricelqui, U., Bigas, C., & Benitah, S. A. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.09.023 · Cited by 600
Cell motility in cancer invasion and metastasis: insights from simple model organisms
Stuelten, C. H., Parent, C. A., & Montell, D. J. (2018) · Nature reviews. Cancer · doi:10.1038/nrc.2018.15 · Cited by 526
Won, S. J., Kit, M. C. S., & Martin, B. R. (2017) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2017.1409191 · Cited by 199
Self-citationCell polarity signaling in the plasticity of cancer cell invasiveness
Gandalovičová, A., Vomastek, T., Rösel, D., & Brábek, J. (2016) · Oncotarget · doi:10.18632/oncotarget.7214 · Cited by 156
Scribble: A master scaffold in polarity, adhesion, synaptogenesis, and proliferation
Bonello, T. T., & Peifer, M. (2019) · Journal of Cell Biology · doi:10.1083/jcb.201810103 · Cited by 127
“Similarly, conditional mammary gland knockout did not disrupt initial gland architecture but at maturity led to ductal hyperplasia (Godde et al., 2014), a phenotype mimicked by an LRR point mutant (Feigin et al., 2014).”
Background
Metadata
- Authors
- Feigin, M. E., Akshinthala, S. D., Araki, K., Rosenberg, A. Z., Muthuswamy, L. B., Martin, B., Lehmann, B. D., Berman, H. K., Pietenpol, J. A., Cardiff, R. D., & Muthuswamy, S. K.
- Affiliations
- Ontario Institute for Cancer Research (CA)
- Corresponding author
- Muthuswamy, Senthil K.
- ORCID
- Venue
- Cancer Research
- Published
- 2014-05-29
- Volume
- 74
- Issue
- 11
- Pages
- 3180-3194
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC4096808
- OpenAlex
- W2107089643
- Cited by
- 135
- References
- 49
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 5 · 2023: 11 · 2022: 15 · 2021: 6 · 2020: 9 · 2019: 14 · 2018: 11 · 2017: 16 · 2016: 16 · 2015: 11 · 2014: 4
- FWCI
- 6.43
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Cancer Institute (CA105388, U01CA105388, CA098830, R56CA098830, P30CA093373, R01CA098830)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
- Keywords
- Scribble, SCRIB, breast cancer, basal-like breast cancer, cell polarity, cell-cell contact, protein mislocalization, PTEN, PI3K signaling, mammary carcinogenesis, tumor suppressor, epithelial differentiation, transgenic mice
- MeSH terms
- Animals, Breast Neoplasms, Cell Line, Female, Humans, Membrane Proteins, Mice, Transgenic, Signal Transduction, Gene Expression, Cell Polarity, Phosphatidylinositol 3-Kinases, Tumor Suppressor Proteins, Cell Line, Tumor, Proto-Oncogene Proteins c-akt, PTEN Phosphohydrolase, Mice, HEK293 Cells, Class I Phosphatidylinositol 3-Kinases, TOR Serine-Threonine Kinases, Carcinogenesis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-09-30, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-09-30 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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