Stem cell antigen-1 enhances tumorigenicity by disruption of growth differentiation factor-10 (GDF10)–dependent TGF-β signaling
Open accessAbstract
Stem cell antigen (Sca)-1/Ly6A, a glycerophosphatidylinositol-linked surface protein, was found to be associated with murine stem cell– and progenitor cell–enriched populations, and also has been linked to the capacity of tumor-initiating cells. Despite these interesting associations, this protein's functional role in these processes remains largely unknown. To identify the mechanism underlying the protein's possible role in mammary tumorigenesis, Sca-1 expression was examined in Sca-1 +/EGFP mice during carcinogenesis. Mammary tumor cells derived from these mice readily engrafted in syngeneic mice, and tumor growth was markedly inhibited on down-regulation of Sca-1 expression. The latter effect was associated with significantly elevated expression of the TGF-β ligand growth differentiation factor-10 (GDF10), which was found to selectively activate TGF-β receptor (TβRI/II)-dependent Smad3 phosphorylation. Overexpression of GDF10 attenuated tumor formation; conversely, silencing of GDF10 expression reversed these effects. Sca-1 attenuated GDF10-dependent TGF-β signaling by disrupting the heterodimerization of TβRI and TβRII receptors. These findings suggest a new functional role for Sca-1 in maintaining tumorigenicity, in part by acting as a potent suppressor of TGF-β signaling.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Unlike other GDFs, GDF10 signals through TGFβRI and RII and downstream transcription factors Smad2/3, and not BMPRI/II and Smad1/5.
“Unlike other GDFs, GDF10 signals through TGFβRI and RII and downstream transcription factors Smad2/3, and not BMPRI/II and Smad1/515”
From GDF10 is a signal for axonal sprouting and functional recovery after stroke (2015) · cites this paper as [15]
The Results (Fig. 3A, F–G) show that GDF10 requires TβRI and TβRII for Smad3 activation and induces nuclear localization of Smad2/3, but not Smad1/5. The paper does not establish that GDF10 never signals through BMP receptors or that its pathway differs from those of all other GDFs. (LLM, conf=0.88)
Experimental — accuracy not yet measuredGDF10 signals through TGFβ receptors.
“and signals through TGFβ receptors (TGFβR)14,15.”
From GDF10 is a signal for axonal sprouting and functional recovery after stroke (2015) · cites this paper as [15]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
No citation lists for this paper
No citation lists for this paper yet — checked again daily.
References 47 · Cited by 75
Research works printed but not linked: 3
- [5]Seigel GM, Hackam AS, Ganguly A, Mandell LM, Gonzalez-Fernandez F. Human embryonic and neuronal stem cell markers in retinoblastoma. Mol Vis. 2007;13:823–832. [PMC free article] [PubMed] [Google Scholar]
- [19]Massagué J, Like B. Cellular receptors for type β transforming growth factor: Ligand binding and affinity labeling in human and rodent cell lines. J Biol Chem. 1985;260:2636–2645. [PubMed] [Google Scholar]
- [40]Nieuwenhuis EJ, et al. Quantitative molecular detection of minimal residual head and neck cancer in lymph node aspirates. Clin Cancer Res. 2003;9:755–761. [PubMed] [Google Scholar]
- Authors
- Upadhyay, G., Yin, Y., Yuan, H., Li, X., Derynck, R., & Glazer, R. I.
- Affiliations
- Georgetown University Medical Center (US)
- Georgetown Lombardi Comprehensive Cancer Center (US)
- University of California, San Francisco (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2011-04-25
- Volume
- 108
- Issue
- 19
- Pages
- 7820-7825
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3093514
- OpenAlex
- W2048121294
- Cited by
- 75
- References
- 47
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 4 · 2023: 8 · 2022: 4 · 2021: 4 · 2020: 6 · 2019: 5 · 2018: 7 · 2017: 3 · 2016: 6 · 2015: 5 · 2013: 7 · 2012: 6
- FWCI
- 2.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Chinese Academy of Agricultural Sciences
- National Institutes of Health (1s10rr019291-01a2, n01cn43309-10-0-1)
- National Cancer Institute (N01 CN043309, R01CA136690, R01CA111482, P30CA051008)
- National Center for Research Resources (1 S10 RR019291-01A2, C06RR014567, S10 RR019291)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- Sca-1, GDF10, TGF-beta signaling, Smad3 phosphorylation, mammary carcinogenesis, cancer stem cells, tumor suppressor, tumor engraftment
- MeSH terms
- Receptor, Transforming Growth Factor-beta Type I, Receptor, Transforming Growth Factor-beta Type II, Animals, Antigens, Ly, Base Sequence, Female, Mammary Neoplasms, Experimental, Membrane Proteins, Mice, Inbred C57BL, Mice, Transgenic, Models, Biological, RNA, Messenger, RNA, Neoplasm, Signal Transduction, Gene Expression Regulation, Neoplastic, Transforming Growth Factor beta, Protein Serine-Threonine Kinases, Receptors, Transforming Growth Factor beta, Mice, Knockout, Green Fluorescent Proteins, Mice, Smad3 Protein, Growth Differentiation Factor 10
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.
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.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
