The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index; 24 of the 29 sources its claims cite were checked for support.
Chromosomal instability drives metastasis through a cytosolic DNA response
Open accessAbstract
Chromosomal instability is a hallmark of cancer that results from ongoing errors in chromosome segregation during mitosis. Although chromosomal instability is a major driver of tumour evolution, its role in metastasis has not been established. Here we show that chromosomal instability promotes metastasis by sustaining a tumour cell-autonomous response to cytosolic DNA. Errors in chromosome segregation create a preponderance of micronuclei whose rupture spills genomic DNA into the cytosol. This leads to the activation of the cGAS-STING (cyclic GMP-AMP synthase-stimulator of interferon genes) cytosolic DNA-sensing pathway and downstream noncanonical NF-κB signalling. Genetic suppression of chromosomal instability markedly delays metastasis even in highly aneuploid tumour models, whereas continuous chromosome segregation errors promote cellular invasion and metastasis in a STING-dependent manner. By subverting lethal epithelial responses to cytosolic DNA, chromosomally unstable tumour cells co-opt chronic activation of innate immune pathways to spread to distant organs.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
63 Own result · 15 Own interpretation · 11 Own method · 9 Partly supported · 6 Supported · 2 No full text of the sources · 1 Couldn’t confirm · 1 Sources not found · 1 No basis given · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Chromosomally unstable cells exhibit evidence of chromosome missegregation during anaphase3,4”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > Abstract
What the sources say
- Supportedcites [3] Thompson, S. L. & Compton, D. A. Examining the link between chromosomal instability and aneuploidy in human cells. J. Cell Biol. 180, 665–672 (2008) source
The Results and discussion section reports lagging chromatids during anaphase in chromosomally unstable cell lines, identifying them as the most common mitotic defect observed. It also reports more lagging chromatids per anaphase in unstable than in stable cells. Page numbers are not provided in our copy. (LLM, conf=0.94)
- Partly supportedcites [4] Cimini, D. et al. Merotelic kinetochore orientation is a major mechanism of aneuploidy in mitotic mammalian tissue cells. J. Cell Biol. 153, 517–527 (2001) sourceExperimental — accuracy not yet measured
The Results section reports lagging chromosomes and occasional sister-chromatid missegregation during anaphase in PtK1 cells. It does not establish that the cells studied were chromosomally unstable, so the claim’s population qualifier is not supported by this paper. (LLM, conf=0.84)
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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“we overexpressed Kif2a, a third member of the kinesin-13 proteins that lacks kinetochore and centromere localization domains13, and observed no effect on CIN despite exhibiting microtubule-depolymerizing activity on interphase microtubules”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > CIN is a driver of metastasis
What the sources say
- Partly supportedcites [13] Ems-McClung, S. C. & Walczak, C. E. Kinesin-13s in mitosis: key players in the spatial and temporal organization of spindle microtubules. Semin. Cell Dev. Biol. 21, 276–282 (2010) sourceExperimental — accuracy not yet measured
The citation is attached to the description of Kif2A, not to the citing authors’ own overexpression and CIN results. Section 3.1 identifies Kif2A as a kinesin-13 found mainly at spindle poles, but also reports its association with centromeres; the copy does not establish that it lacks kinetochore and centromere localization domains. The cited review does not report the stated overexpression experiment. (LLM, conf=0.75)
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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Destabilization of microtubule attachments to chromosomes at the kinetochores, through overexpression of the non-motile microtubule depolymerizing kinesin-13 proteins, Kif2b or MCAK/Kif2c, directly suppresses CIN in otherwise chromosomally unstable cells5–7.”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > Abstract
What the sources say
- Partly supportedcites [5] Bakhoum, S. F. et al. The mitotic origin of chromosomal instability. Curr. Biol. 24, R148–R149 (2014) sourceExperimental — accuracy not yet measured
In the main text (page unavailable), GFP–Kif2b overexpression reduced karyotypic heterogeneity in two CIN+ cell lines, supporting suppression of CIN. The paper also reports earlier results for kinesin-13 overexpression in two other CIN+ lines, but our copy does not identify MCAK/Kif2c or establish its effect separately. (LLM, conf=0.88)
- Supportedcites [6] Bakhoum, S. F. et al. Numerical chromosomal instability mediates susceptibility to radiation treatment. Nat. Commun. 6, 5990 (2015) source
In Results, “Extra-nuclear DNA damage in irradiated mitotic cells” (page unavailable), the paper reports that Kif2b overexpression reduced chromosome segregation errors in chromosomally unstable U251 cells by destabilizing kinetochore–microtubule attachments. In Results, “w-CIN influences viability of irradiated mitotic cells” (page unavailable), it also identifies MCAK overexpression as suppressing whole-chromosome CIN, albeit in a slightly different manner. (LLM, conf=0.92)
- Supportedcites [7] Bakhoum, S. F., Thompson, S. L., Manning, A. L. & Compton, D. A. Genome stability is ensured by temporal control of kinetochore–microtubule dynamics. Nat. Cell Biol. 11, 27–35 (2009) source
The ‘Suppression of chromosomal instability’ section reports that GFP-Kif2b or GFP-MCAK overexpression reduces chromosome mis-segregation and suppresses CIN in the unstable U2OS and MCF-7 cell lines. It attributes this effect to increased kinetochore–microtubule turnover that releases inappropriate attachments. (LLM, conf=0.95)
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.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“whereas overexpression of a dominant negative MCAK mutant12 (dnMCAK) led to a modest increase in chromosome missegregation in MDA-MB-231 cells.”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > CIN is a driver of metastasis
What the sources say
- Supportedcites [12] Moore, A. T. et al. MCAK associates with the tips of polymerizing microtubules. J. Cell Biol. 169, 391–397 (2005) source
The citation is attached to the MCAK mutant, rather than to the citing paper’s result in MDA-MB-231 cells. In Results and discussion (Fig. 2; page not given), the source identifies and uses GFP-hypir-MCAK, a motor-domain mutant inactive in microtubule depolymerization. It does not report the chromosome-missegregation result. (LLM, conf=0.86)
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.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Cells overexpressing Kif2b or MCAK continue to propagate abnormal aneuploid karyotypes albeit in a stable manner7.”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > Abstract
What the sources say
- Supportedcites [7] Bakhoum, S. F., Thompson, S. L., Manning, A. L. & Compton, D. A. Genome stability is ensured by temporal control of kinetochore–microtubule dynamics. Nat. Cell Biol. 11, 27–35 (2009) source
The ‘Suppression of chromosomal instability’ section reports that U2OS clones overexpressing GFP-Kif2b or GFP-MCAK retained their aneuploid modal chromosome numbers while showing reduced deviations from those numbers. Those reductions persisted for 50 generations, supporting stable propagation of abnormal karyotypes. (LLM, conf=0.93)
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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Chromosomal instability (CIN) correlates with tumor metastasis1,2”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > Abstract
What the sources say
- Partly supportedcites [1] Jamal-Hanjani, M. et al. Tracking the evolution of non-small-cell lung cancer. N. Engl. J. Med. 376, 2109–2121 (2017) sourceExperimental — accuracy not yet measured
The Results passage (page not available in our copy) links a high proportion of subclonal copy-number alterations to a higher risk of recurrence or death in patients with non–small-cell lung cancer. The Discussion describes copy-number heterogeneity in relation to chromosomal instability, but neither passage establishes a correlation with metastasis specifically. (LLM, conf=0.84)
- Not checked — no full text of the sourcecites [2] Turajlic, S. & Swanton, C. Metastasis as an evolutionary process. Science 352, 169–175 (2016) 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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“We found a striking localization of cGAS to approximately half of all micronuclei as previously observed22,23.”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > Metastasis from cytosolic DNA response
What the sources say
- Partly supportedcites [22] Harding, S. M. et al. Mitotic progression following DNA damage enables pattern recognition within micronuclei. Nature 548, 466–470 (2017) sourceExperimental — accuracy not yet measured
The section labeled Abstract (page not provided) reports that cGAS localizes to micronuclei, and Extended Data Figure 4 describes measuring cGAS-positive micronuclei. However, the passages do not report that approximately half of all micronuclei are cGAS-positive. The reported majority concerns micronucleated daughter cells in a live-imaging experiment, not all micronuclei. (LLM, conf=0.85)
- Partly supportedcites [23] Mackenzie, K. J. et al. cGAS surveillance of micronuclei links genome instability to innate immunity. Nature 548, 461–465 (2017) sourceExperimental — accuracy not yet measured
The paper reports that cGAS localizes to micronuclei, but its quantified result is 83.3 ± 1.4% GFP-cGAS-positive micronuclei in RNase H2-deficient mouse fibroblasts (Abstract, Fig. 1d), not approximately half. It also describes localization in other settings without establishing a proportion for all micronuclei. (LLM, conf=0.88)
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.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Impeding micronuclear rupture through Lamin B2 overexpression20 significantly diminished the relative fraction of cGAS+ micronuclei (Fig. 6a–b).”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > Metastasis from cytosolic DNA response
What the sources say
- Supportedcites [20] Hatch, E. M., Fischer, A. H., Deerinck, T. J. & Hetzer, M. W. Catastrophic nuclear envelope collapse in cancer cell micronuclei. Cell 154, 47–60 (2013) source
The Results section (“NE collapse is triggered by lamin disorganization”) reports significantly more intact micronuclei after Lamin B2 overexpression and concludes that increased lamin B can prevent micronuclear disruption. Citation 20 is attached to that intervention; the decrease in cGAS-positive micronuclei is presented as the citing paper’s own Figure 6a–b result. (LLM, conf=0.92)
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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The top 23 differentially expressed genes in CIN-high cells (referred to as CIN signature) predicted distant-metastasis-free survival (DMFS) in a meta-analysis16 as well as a validation cohort17 of patients with breast cancer, irrespective of tumor subtype, grade, or lymph node status”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > CIN enriches for mesenchymal traits
What the sources say
- Partly supportedcites [16] Györffy, B. et al. An online survival analysis tool to rapidly assess the effect of 22,277 genes on breast cancer prognosis using microarray data of 1,809 patients. Breast Cancer Res. Treat. 123, 725–731 (2010) sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.
- Could not verifycites [17] Hatzis, C. et al. A genomic predictor of response and survival following taxane–anthracycline chemotherapy for invasive breast cancer. J. Am. Med. Assoc. 305, 1873–1881 (2011) sourceExperimental — accuracy not yet measured
The Methods describe predictors using 33 and 27 probe sets for early relapse, not a 23-gene CIN signature. The Results report distant-relapse-free survival in an independent validation cohort, but our copy does not say that the CIN signature was tested there or that it predicted survival irrespective of subtype, grade, or lymph-node status. Searches for the CIN signature and those validation claims found no supporting passage; page numbers were unavailable. (LLM, conf=0.76)
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.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“These two mutually exclusive states, which were recently observed in a pan-cancer genomic analysis of metastatic tumors41, likely account for the reversibility in chromosome missegregation rates seen in primary tumors and metastases”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > DISCUSSION
What the sources say
- Supportedcites [41] Robinson, D. R. et al. Integrative clinical genomics of metastatic cancer. Nature 548, 297–303 (2017) source
The citation is attached to the observation of two mutually exclusive states, not to the citing authors’ proposed explanation for reversible chromosome missegregation rates. In “Transcriptional signatures of metastatic disease,” the source identifies two metastatic-tumor subtypes and reports mutual exclusivity between their proliferative and EMT gene sets. (LLM, conf=0.93)
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.
- Supported
- It may state two separate claims as one. 32
- Probably not a substantial claim. 13
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Overexpression of the spindle assembly checkpoint protein, Mad2 in MCAK-expressing cells partially rescued chromosome missegregation15, and correspondingly augmented metastasis”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > CIN is a driver of metastasis
What the sources say
- Could not verifycites [15] Sotillo, R. et al. Mad2 overexpression promotes aneuploidy and tumorigenesis in mice. Cancer Cell 11, 9–23 (2007) sourceExperimental — accuracy not yet measured
The Summary (p. 1) and the chromosomal-instability results (p. 5) describe Mad2 overexpression in mice and fibroblasts, not in MCAK-expressing cells. Searches for MCAK, rescue of missegregation, and metastasis found no passage addressing those claimed outcomes. The reported increase in segregation defects without MCAK does not establish what happens when MCAK is expressed. (LLM, conf=0.75)
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.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Suppressing micronuclear envelope rupture through mCherry-Lamin B2 overexpression20 reduced cytosolic dsDNA staining without influencing chromosome segregation errors.”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > CIN generates cytosolic DNA
What the sources say
- Partly supportedcites [20] Hatch, E. M., Fischer, A. H., Deerinck, T. J. & Hetzer, M. W. Catastrophic nuclear envelope collapse in cancer cell micronuclei. Cell 154, 47–60 (2013) sourceExperimental — accuracy not yet measured
The Results section, “NE collapse is triggered by lamin disorganization” (page unavailable), reports that LmnB2 expression increased the proportion of intact micronuclei. It does not report reduced cytosolic dsDNA staining or test whether LmnB2 overexpression affects chromosome segregation errors. A separate Results passage finds no significant effect of micronuclear disruption on micronucleus formation after a second mitosis, but that is not the stated overexpression comparison. (LLM, conf=0.88)
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.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“We found evidence for noncanonical NF-κB activation in CIN-high cells as revealed by lower levels of the precursor protein, p100, a trend toward higher ratios of p52 and phosphorylated p100 relative to total p100, as well as lower levels of the noncanonical NF-κB pathway inhibitor, TRAF231”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > Metastasis from cytosolic DNA response
What the sources say
- Supportedcites [31] Sun, S.-C. Controlling the fate of NIK: a central stage in noncanonical NF-κB signaling. Sci. Signal. 3, pe18 (2010) source
The cited paper supplies the mechanistic basis for interpreting the citing authors’ measurements: it describes p100 as the precursor of p52, phosphorylation and processing of p100 during noncanonical NF-κB activation, and TRAF2-dependent restraint of that pathway (passages 1, 2, and 6). The CIN-high measurements are presented as the citing authors’ own findings, not as findings attributed to this source. (LLM, conf=0.90)
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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“These findings are in line with reported roles for the noncanonical NF-κB pathway in EMT, cellular invasion, and metastasis33–35.”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > Metastasis from cytosolic DNA response
What the sources say
- Partly supportedcites [33] Wang, X. et al. Oestrogen signalling inhibits invasive phenotype by repressing RelB and its target BCL2. Nat. Cell Biol. 9, 470–478 (2007) sourceExperimental — accuracy not yet measured
The Abstract reports that RelB promotes EMT and an invasive phenotype in breast cancer cells. It discusses metastasis through prior findings about NF-κB and Bcl-2, and calls for future studies of RelB in metastatic breast disease; it does not establish a role for the RelB pathway in metastasis. (LLM, conf=0.84)
- Partly supportedcites [34] Wang, J., Yi, S., Zhou, J., Zhang, Y. & Guo, F. The NF-κB subunit RelB regulates the migration and invasion abilities and the radio-sensitivity of prostate cancer cells. Int. J. Oncol. 49, 381–392 (2016) sourceExperimental — accuracy not yet measured
The Discussion (p. 10) reports a role for RelB, a noncanonical NF-κB subunit, in EMT in breast cancer cells and shows that RelB knockdown reduced invasion in prostate cancer cells. It discusses links to metastasis, but does not establish that RelB itself promotes metastasis; the authors say in vivo studies remain for future work (Discussion, p. 11). (LLM, conf=0.86)
- Partly supportedcites [35] Yang, C. et al. Antagonism of inhibitor of apoptosis proteins increases bone metastasis via unexpected osteoclast activation. Cancer Discov. 3, 212–223 (2013) sourceExperimental — accuracy not yet measured
The Results section ('Osteoclast expression of constitutively active NIK promotes tumor growth in bone'; page unavailable) links activation of the alternative NF-κB pathway in osteoclasts to increased tumor burden in bone. The Discussion likewise describes promotion of metastatic growth through osteoclast activity. These passages support a role in bone metastatic growth, but do not establish roles in EMT or cellular invasion. (LLM, conf=0.85)
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.
- Partly supported
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
“Kinesin-13 overexpression did not alter cellular proliferation or the number of centrosomes per cell (Fig. 2a–b, Extended Data Figs. 1f–h and 3a).”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > CIN is a driver of metastasis
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
“Importantly, CIN-low cells maintained highly aneuploid karyotypes, yet they faithfully propagated them in a stable manner.”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > CIN is a driver of metastasis
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
“whereas metastases from CIN-high cells involved multiple organs and rapidly progressed leading to death.”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > CIN is a driver of metastasis
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
“as evidenced by reduction in metastatic dissemination, lifespan extension, and reduction in in vitro and in vivo invasion in CIN-high cells depleted of STING, RelB, or p100 (NFKB2).”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > Metastasis from cytosolic DNA response
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
“whereas the addition of cGAMP or overexpression of Mad2 increased nuclear RelB in MCAK-expressing cells (Fig. 6d, Extended Data Figs. 4e and 9c–e).”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > Metastasis from cytosolic DNA response
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
“Karyotype analysis revealed that the injected cell lines and most metastases had three copies of chromosome 1, whereas primary tumors consistently had 2 copies.”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > CIN enriches for mesenchymal traits
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
“Indeed, induced missegregation of the Y chromosome led to the upregulation of OAS2, an ISG, and increased interferon-β production by DLD-1 cells (Extended Data Fig. 9f–g).”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > Metastasis from cytosolic DNA response
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
“Conversely, mice injected with CIN-low cells exhibited lower metastatic burden and a median survival of 207 days.”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > CIN is a driver of metastasis
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
“STING depletion reduced RelB nuclear localization and led to downregulation of EMT and inflammatory pathways”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > Metastasis from cytosolic DNA response
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
“The dsDNA signal, which was distinct from mitochondrial staining, disappeared after treatment with double-strand-specific – but not single-strand-specific – nuclease and after overexpression of Dnase2, confirming the specificity of these antibodies”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > CIN generates cytosolic DNA
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
“Suppression of CIN had no effect on primary tumor implantation efficiency and even enhanced primary tumor growth in the 4T1 model.”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > CIN is a driver of metastasis
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
“Strikingly, Y chromosome-specific fragments were found dispersed within the cytosol 2–3 days after Dox/IAA addition, whereas the control autosome remained confined to the nucleus (Fig. 5h), demonstrating that cytosolic DNA is generated from chromosomes undergoing high rates of missegregation”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > CIN generates cytosolic DNA
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.
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
“Yet, in both models, suppression of CIN significantly reduced spontaneous metastasis and prolonged survival (Extended Data Fig. 3d–e).”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > CIN is a driver of metastasis
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
“we performed a gene-gene Pearson correlation analysis using scRNA-seq data and identified two large gene modules: module 1 was characterized by proliferative and metabolic pathways, whereas module 2 comprised EMT and inflammation gene sets”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > CIN generates cytosolic DNA
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
“We ruled out a direct role for kinesin-13-mediated microtubule depolymerization in activating small GTPases14 by performing RhoA and Rac1 pull-down assays, which revealed low basal levels of activity and no correlation with kinesin-13 overexpression”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > CIN is a driver of metastasis
What the sources say
- Not checked — no full text of the sourcecites [14] Waterman-Storer, C. M., Worthylake, R. A., Liu, B. P., Burridge, K. & Salmon, E. D. Microtubule growth activates Rac1 to promote lamellipodial protrusion in fibroblasts. Nat. Cell Biol. 1, 45–50 (1999) source
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
“Principle component analysis (PCA) and unsupervised clustering accurately separated samples according to their CIN status.”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > CIN enriches for mesenchymal traits
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.
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
“There was a robust correlation between the CIN signature, STING, and the CIN-responsive NC-NF-κB genes in scRNA-seq data, in contrast to a weaker correlation between CIN and type I interferon targets”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > Metastasis from cytosolic DNA response
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
“Conversely, increased canonical NF-κB or type I interferon regulatory factors were associated with an improved prognosis (Extended Data Fig. 10a).”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > Metastasis from cytosolic DNA response
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.
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 stained cells using two different anti-dsDNA antibodies after selective plasma membrane permeabilization and found increased cytosolic dsDNA and single-stranded DNA (ssDNA) in CIN-high cells.”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > CIN generates cytosolic DNA
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
“CIN-high cells and those derived from metastases exhibited a higher preponderance of micronuclei compared with CIN-low or primary tumor-derived cells, respectively”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > CIN generates cytosolic DNA
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
“and displayed evidence of actin cytoskeletal reorganization, diffuse vimentin staining, and increased cytoplasmic and nuclear localization of β-catenin (Extended Data Figs. 6c–d and 7a–d).”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > CIN enriches for mesenchymal traits
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
“Yet, metastases contained a large number of differentially upregulated EMT and inflammation-related genes that were disproportionately clustered on chromosome 1, signifying chromosome 1-specific selection.”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > CIN enriches for mesenchymal traits
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
“Changes in β-catenin are seen upon alteration of CIN; enriched at cell-to-cell junctions in MCAK expressing cells but cytoplasmic and nuclear in dnMCAK expressing cells”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > Extended Data
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.
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
“This leads to the activation of the cGAS-STING cytosolic DNA-sensing pathway and downstream noncanonical NF-κB signaling.”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > 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 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
“CIN generates micronuclei and cytosolic DNA”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > Extended Data
plaindirectn = 44- 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“There was no need to randomize animals.”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > METHODS > Animal studies
plain- 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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Diploid controls were used to determine false positive rate of the centromeric probes.”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > Extended Data
plain- 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Investigators were not blinded to group allocation.”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > METHODS > Animal studies
plain- 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All cells tested negative for mycoplasma.”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > METHODS > Cell culture
plain- 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
“ongoing chromosome missegregation is required to replenish cytosolic DNA pools and to maintain cells in a pro-metastatic state.”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > 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.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For each probe, three normal peripheral blood samples (GM07535, GM06875 and GM00558), obtained from Coriell Institute (Camden, New Jersey) were also analyzed to derive cut-off values (false-positive).”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > METHODS > Fluorescence in situ hybridization (FISH) analysis
plainn = 3- 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
“CIN promotes formation and maintenance of metastasis”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > Extended Data
plaindirectn = 2- 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For each sample a minimum of 20 inverted DAPI-stained metaphases were fully karyotyped and analyzed according to the International System of Human Cytogenetic Nomenclature (ISCN) 2013.”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > METHODS > Single-cell karyotyping
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.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Our analysis was robust to imputation and we obtained similar results without imputed data (not shown).”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > METHODS > Single-cell RNA sequencing
plain- 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For the 4T1 experiments, Power analysis indicates that 10 mice per group will be sufficient to detect a difference at relative hazard ratios of <0.25 or >4.0 with 80% power and 95% confidence, given a median survival of 58 days in the control group and a total follow up period of 180 days.”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > METHODS > Animal studies
hedgedn = 10- 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Additionally, to minimize the effects of experimental artifacts on the analysis, data was pre-processed to filter out cells with low total molecule counts (library size), low complexity and high mitochondrial content, identified by a bimodal fit.”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > METHODS > Single-cell RNA sequencing
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
“The evolutionary benefits of the noncanonical pathway would justify the scarcity of inactivating mutations in cGAS and STING among breast and lung cancers (Extended Data Fig. 10e).”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > DISCUSSION
hedgeddirect- 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For disease-specific survival in MDA-MB-231 experiments, power analysis indicated that 10 mice per group will be sufficient to detect a difference at relative hazard ratios of <0.2 or >5 with 80% power and 95% confidence, given a median disease-specific survival of 3 months in the control group and a total follow up period of 250 days.”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > METHODS > Animal studies
hedgedn = 10- 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Mitochondria were purified at 12,000xg to minimize their contamination in the cytosolic fraction.”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > METHODS > Quantification of cytosolic DNA
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
“CIN promotes in vitro invasion and migration”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > Extended Data
plaindirectn = 4- 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.
The paper relies on this without support.
The role of CIN in metastasis has not been established.
“its role in metastasis has not been established.”
The paper relies on this without support.
The mouse xenograft and orthotopic models recapitulate human metastatic progression sufficiently to infer CIN's role in human metastasis.
“We injected MDA-MB-231 cells into the left cardiac ventricles of athymic mice to enable systemic dissemination while tracking metastatic colonization using a bioluminescence reporter.”
The paper relies on this without support.
The human tumor cohorts analyzed are representative of human metastatic disease generally.
“we applied the weighted-genomic integrity index (wGII) as a proxy for CIN8 on 79 primary tumor-brain metastases matched pairs from a recently published cohort9.”
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?
In the citing paper
“While MN have been proposed to activate as tumor suppressor pathways, MN also play a critical pathogenic role in the evolution of cancer genomes and metastasis by driving genomic instability through chromothripsis (Bakhoum et al., 2018; Umbreit et al., 2020; Ye et al., 2019; Zhang et al., 2015).”
From Cytoplasmic DNA: sources, sensing, and role in aging and disease (2021) · cites this paper as Bakhoum et al., 2018
In the citing paper
“Moreover, STING-dependent activation of noncanonical NF-κB signaling, due to ruptured MN, promotes metastasis (Bakhoum et al., 2018).”
From Cytoplasmic DNA: sources, sensing, and role in aging and disease (2021) · cites this paper as Bakhoum et al., 2018
In the citing paper
“For example, in breast and lung cancers, suppression of chromosomal instability and associated cytoDNA decreases metastasis (Bakhoum et al., 2018).”
From Cytoplasmic DNA: sources, sensing, and role in aging and disease (2021) · cites this paper as Bakhoum et al., 2018
In the citing paper
“Researchers have observed differences in the expression of essential genes in the cGAS‐STING signaling mechanism between normal and malignant tissues, along with MB21D1‐encoding cGAS, transmembrane protein 173 (TMEM‐173)‐encoding STING, TANK‐binding kinase 1 (TBK‐1) and interferon regulatory factor 3 (IRF‐3).”
From Tumor microenvironment signaling and therapeutics in cancer progression (2023) · cites this paper as [253]
In the citing paper
“Comprehensive research and recent evidence proved that these four genes were significantly elevated in almost all cancer models, suggesting that cGAS‐STING signal transduction might be stimulated in all cancer types [252, 253].”
From Tumor microenvironment signaling and therapeutics in cancer progression (2023) · cites this paper as [253]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Chromosomal instability drives metastasis through a cytosolic DNA response > Metastasis from cytosolic DNA response
“a trend toward higher ratios of p52 and phosphorylated p100 relative to total p100”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > Extended Data
“Normalized ratio of phosphorylated p52-to-p100 (left) and p100-to-total p100 (right) protein levels.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Chromosomal instability drives metastasis through a cytosolic DNA response > METHODS > Single-cell RNA sequencing
“A unique sample index for each library was introduced through 10 cycles of PCR amplification”
§ Chromosomal instability drives metastasis through a cytosolic DNA response > METHODS > Single-cell RNA sequencing
“(98°C for 45 s; 98°C for 20s, 60°C for 30s, and 72°C for 20 s x 14 cycles; 72°C for 1min; held at 4°C).”
Citations
Cites
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709
HTSeq—a Python framework to work with high-throughput sequencing data
Anders, S., Pyl, P. T., & Huber, W. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btu638 · Cited by 21,464
Trapnell, C., Williams, B. A., Pertea, G., Mortazavi, A., Kwan, G., van Baren, M. J., Salzberg, S. L., Wold, B. J., & Pachter, L. (2010) · Nature Biotechnology · doi:10.1038/nbt.1621 · Cited by 15,556
Massively parallel digital transcriptional profiling of single cells
Zheng, G. X. Y., Terry, J. M., Belgrader, P., Ryvkin, P., Bent, Z. W., Wilson, R., Ziraldo, S. B., Wheeler, T. D., McDermott, G. P., Zhu, J., et al. (2017) · Nature Communications · doi:10.1038/ncomms14049 · Cited by 7,353
Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway
Sun, L., Wu, J., Du, F., Chen, X., & Chen, Z. J. (2013) · Science · doi:10.1126/science.1232458 · Cited by 4,996
circlize implements and enhances circular visualization in R
Gu, Z., Gu, L., Eils, R., Schlesner, M., & Brors, B. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu393 · Cited by 4,290
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
Nextflow enables reproducible computational workflows
Di Tommaso, P., Chatzou, M., Floden, E. W., Barja, P. P., Palumbo, E., & Notredame, C. (2017) · Nature Biotechnology · doi:10.1038/nbt.3820 · Cited by 4,001
Cited by
Sorted by citations
Items 1,001–1,100 of 1,551
Au naturale: use of biologically derived cyclic di-nucleotides for cancer immunotherapy
Waters, C. M. (2021) · Open Biology · doi:10.1098/rsob.210277 · Cited by 6
Yu, H. G., Bijian, K., da Silva, S. D., Su, J., Morand, G. B., Spatz, A., & Alaoui‐Jamali, M. A. (2022) · Oncogene · doi:10.1038/s41388-022-02317-7 · Cited by 7
“Micronuclei-induced STING activation occurs due to micronuclei membrane rupture and subsequent recruitment of cGAS to those micronuclei [20, 59, 60].”
BackgroundWang, P., Zhang, Q., Han, L., Cheng, Y., Sun, Z., Yin, Q., Zhang, Z., & Yu, J. (2022) · Cancers · doi:10.3390/cancers14205028 · Cited by 6
“GI is associated with disease staging, metastasis, poor prognosis, and treatment resistance [7,8].”
BackgroundSystematic pan-cancer analysis identifies cGAS as an immunological and prognostic biomarker
Chen, P., Yang, X., Wang, P., He, H., Chen, Y., Yu, L., Fang, H., Wang, F., & Huang, Z. (2023) · Annals of Translational Medicine · doi:10.21037/atm-22-6318 · Cited by 5
“This mechanism may be that COVID-19 activates cGAS /STING and then activates its downstream noncanonical nuclear factor-κ B (NF-κ B) signal pathway to promote cancer cell metastasis (21).”
Pickering, S., Sumner, J., Kerridge, C., Perera, M. R., & Neil, S. J. D. (2023) · mBio · doi:10.1128/mbio.03293-22 · Cited by 6
RB1 aberrations predict outcomes of immune checkpoint inhibitor combination therapy in NSCLC
Wang, Q., Yu, T., Ke, Z., Wang, F.-F., Yin, J. C., Shao, Y. W., & Lu, K. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1172728 · Cited by 6
“Errors in chromosome segregation create a preponderance of micronuclei, whose rupture spills genomic DNA into the cytosol (48).”
BackgroundMagkouta, S., Vaitsi, P. C., Iliopoulou, M. P., Pappas, A., Kosti, C., Psarra, K., & Kalomenidis, I. (2023) · Cancers · doi:10.3390/cancers15204962 · Cited by 6
“To this end, MTH1 inhibition can be superior to DNA repair targeting agents, since it is vital for the survival of tumor cells without affecting normal cells’ viability, a condition known as phenotypic lethality [34,35].”
BackgroundThe entanglement of DNA damage and pattern recognition receptor signaling
Ha, C. T., Tageldein, M. M., & Harding, S. M. (2023) · DNA repair · doi:10.1016/j.dnarep.2023.103595 · Cited by 6
Aneuploidy-induced cellular behaviors: Insights from Drosophila
Joy, J., Fusari, E., & Milán, M. (2024) · Developmental Cell · doi:10.1016/j.devcel.2023.12.009 · Cited by 6
The reckoning of chromosomal instability: past, present, future
Lynch, A., Bradford, S., & Burkard, M. E. (2024) · Chromosome Research · doi:10.1007/s10577-024-09746-y · Cited by 6
“For instance, cells with higher CIN may be less differentiated (Imreh et al. 2006; Catalina et al. 2008; Gaztelu-mendi and Nogués 2014; Bakhoum et al. 2018 transcriptional plasticity?”
Laryngeal Tumor Microenvironment
Karpathiou, G., Dumollard, J. M., & Péoc’h, M. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-59038-3_5 · Cited by 6
Studying the Role of Chromosomal Instability (CIN) in GI Cancers Using Patient-derived Organoids
Patil, S., Jahagirdar, S., Khot, M., & Sengupta, K. (2021) · Journal of Molecular Biology · doi:10.1016/j.jmb.2021.167256 · Cited by 6
The landscape of enhancer RNA identify prognosis‐related molecular subtypes in gastric cancer
Yan, A., Chen, Y., Bian, R., Wang, C., Que, H., Shen, Y., & Lu, X. (2022) · Cancer Medicine · doi:10.1002/cam4.4959 · Cited by 5
Circulating cell-free DNA and its clinical utility in cancer
Salviano‐Silva, A., Maire, C. L., Lamszus, K., & Ricklefs, F. L. (2022) · Journal of Laboratory Medicine · doi:10.1515/labmed-2022-0047 · Cited by 6
Xu, Y., Wang, X., Guo, B., Wang, D., Kalvakolanu, D. V., Chen, X., Tang, J., Zhang, L., & Yang, Q. (2019) · Human Gene Therapy · doi:10.1089/hum.2019.134 · Cited by 6
Liao, C., Zhao, J., Kumar, S., Chakraborty, C., Talluri, S., Munshi, N. C., & Shammas, M. A. (2020) · Archives of Clinical Toxicology · doi:10.46439/toxicology.2.006 · Cited by 5
“This allows precancerous cells to acquire a variety of new characteristics, some of which then contribute to oncogenic transformation and subsequent progression to advanced disease states and fatal outcome [7,8].”
BackgroundHodgins, J. J., Abou‐Hamad, J., Hagerman, A., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.08.31.506095 · Cited by 6
Mays, J. C., Alfieri, F., Trifas, M., Kogenaru, M., Quysbertf, H. M., Mei, S., Bosco, N., Zhao, X., Bianchi, J. J., Goldberg, A., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.09.08.555746 · Cited by 7
Image-based identification and isolation of micronucleated cells to dissect cellular consequencesPreprint
DiPeso, L., Pendyala, S., Huang, H. Z., Fowler, D. M., & Hatch, E. M. (2024) · eLife · doi:10.7554/elife.101579 · Cited by 6
“We anticipated that this would limit inflammatory signaling and increase the sensitivity of downstream analyses of the consequences of MN formation and rupture (Bakhoum et al., 2018; He et al., 2018; Santaguida et al., 2017).”
An overview of the functions and mechanisms of APOBEC3A in tumorigenesis
Yang, Y., Liu, N., & Gong, L. (2024) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2024.08.020 · Cited by 6
“CIN is a distinguishing feature of human cancers characterized by erroneous chromosomal segregation, resulting in the generation of cytoplasmic dsDNA, which in turn triggers the dsDNA-sensing cGAS e STING pathway response and promotes tumor metastasis 99 .”
Patel, R. K., Parappilly, M. S., Farley, H. C., Latour, E. J., Wang, L. G., Nair, A. M., Lu, E. S., Sims, Z., Park, B. S., Nelson, K., et al. (2024) · Cancers · doi:10.3390/cancers16213650 · Cited by 5
“Multiple mechanisms for hybrid cell formation are proposed [22,27–30], including cellular fusion [20,31,32].”
BackgroundBRCA and Beyond: Impact on Therapeutic Choices Across Cancer
Tan, J. S. H., Zhang, Z., Goh, H. X., & Ngeow, J. Y. Y. (2024) · Cancers · doi:10.3390/cancers17010008 · Cited by 8
“PARPis use also activates the cGAS-STING innate immunity pathway, which results in various immunogenic effects and immune responses [119–121].”
Jèmaà, M., Boubaker, N. S., Kerkeni, N., & Huber, S. M. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26031209 · Cited by 5
“It is interesting to note that several studies have shown that metastatic tumours contain a significant proportion of tetraploid cells compared to primary tumours [11].”
IFNλ1 is a STING-dependent mediator of DNA damage and induces immune activation in lung cancer
Godsk, S. H., Jensen, C. M. S., Larsen, T. V., Ahrenfeldt, J., Gammelgaard, K. R., & Jakobsen, M. R. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1525083 · Cited by 6
“…to promote their growth through the expression of immunomodulatory interferon stimulated genes (ISGs) like PD-L1 (25, 26), or through activation of non-canonical pathways activating NF-k B-dependent transcription of e.g. IL-6 that has been found to be associated with a pro-tumor response (27 – 29).”
Extracellular vesicles in cancer progression: mechanisms and significance
Gao, Y., Wei, D., Zhong, L., Liao, D., Zheng, X., Lin, Y., Fang, D., Chang, B., & Kang, T. (2025) · Science China Life Sciences · doi:10.1007/s11427-024-2852-9 · Cited by 6
Berends, A. M. A., Wardenaar, R., van den Bos, H., Tijhuis, A. E., Links, T. P., Feelders, R. A., Hofland, L. J., Kruijff, S., Pacák, K., Spierings, D. C. J., et al. (2025) · Oncogene · doi:10.1038/s41388-025-03391-3 · Cited by 5
The Hallmarks of Aneuploidy in Cancer and Congenital Syndromes
Cheng, P., Singh, K., Reeves, R. H., & Davoli, T. (2025) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-111723-103557 · Cited by 6
“To this end, two strategies can be employed: identifying CIN-specific effects that disappear when CIN halts but aneuploidy persists (14) and using aneuploid models without CIN to isolate aneuploidy-specific effects.”
Ding, Y., Chen, Y., Zhang, J., Wang, Q., Zhu, S., Jiang, J., He, C., Wang, J., Tou, L., Zheng, J., et al. (2025) · Advanced Science · doi:10.1002/advs.202503499 · Cited by 5
Manda, S. S., Espersen, M. L. M., Mapagu, C., Bouantoun, N., Boros, J., Chiew, Y.-E., Srirangan, S., Pattnaik, S., Kennedy, C. J., Brand, A. H., et al. (2025) · npj Precision Oncology · doi:10.1038/s41698-025-00911-y · Cited by 5
Choi, J., & Jung, M. (2025) · Cancers · doi:10.3390/cancers17183046 · Cited by 5
“DNA-damage-induced inflammatory signaling, particularly non-canonical NF-kB pathway activation, was postulated to accelerate EMT in FA SCCs [24,75].”
Divergent proteome tolerance against gain and loss of chromosome arms
Di, Y., Li, W., Castellano, J. J., Jin, W., Modi, J. N., Šalovská, B., Khosroabadi, D., Hu, W., Taylor, A. M., & Liu, Y. (2025) · Molecular Cell · doi:10.1016/j.molcel.2025.10.023 · Cited by 10
Genetic disruption of mitochondrial dynamics and stasis leads to liver injury and tumorigenesis
Ma, X., Wei, X., Niu, M., Zhang, C., Peng, Z., Liu, W., Yan, J., Su, X., Ma, L., Lu, S., et al. (2025) · Journal of Clinical Investigation · doi:10.1172/jci194441 · Cited by 8
“Additionally, sustained activation of inflammatory signaling in this state exhausts effector immune cells and recruits immunosuppressive cells, collectively creating an immune-suppressive tumor microenvironment that facilitates tumor survival and immune evasion (31, 36–38).”
CRISPR screens define unified hallmarks of cancer cell-autonomous immune evasion
Huber, A., Djajawi, T. M., Rivera, S., Vervoort, S. J., & Kearney, C. J. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116738 · Cited by 5
Huang, H., Chen, Z., Mao, X., Jiang, J., Xi, Y., Wan, Y., Wang, L., Chen, X., & Hu, Y. (2026) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2025-012121 · Cited by 5
“Our TCGA database analysis, along”
Khorramdelazad, H., Arfaei, R., Yaraghi, P., Boroumand, A., Kheyri, A., Shirzad, Z., Kheiri, F., & Bagheri, V. (2026) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2026.105218 · Cited by 5
ER-tethering directs TREX1 penetration of a BAF-dependent barrier at micronuclei
Chen, Y., Norman, R. M., Toufektchan, E., Luan, X., Shim, A., Rosenberg, H., Kovacs, M. T., Nichols, A., Hickling, J. H., Cifani, P., et al. (2026) · Molecular Cell · doi:10.1016/j.molcel.2026.02.012 · Cited by 5
Katavic, S., Cehic, I., Zukic, N., Mirvic, M., Dizdar, M., Gutalj, A., Medić, B. Š., Jerković-Mujkić, A., Mahmutović-Dizdarević, I., & Mešić, A. (2023) · Drug and Chemical Toxicology · doi:10.1080/01480545.2023.2222928 · Cited by 5
“…also make contribution to cellular invasion and/or metastasis. in this regard, the activation of cGas-stiNG signaling, resulting from breakage of the micronuclear membrane following chromosome missegregation, can promote tumor invasion and metastasis in vitro and in vivo (Bakhoum et al .”
BackgroundNovotný, J. P., Mariño‐Enríquez, A., & Fletcher, J. A. (2023) · Cancer treatment and research · doi:10.1007/978-3-031-30065-3_16 · Cited by 5
Pharmacological potential of cyclic nucleotide signaling in immunity
Ednacot, E. M. Q., Nabhani, A., Dinh, D. M., & Morehouse, B. R. (2024) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2024.108653 · Cited by 5
Zhang, X., Huang, N., Mu, Y., Chen, H., Zhu, M., Zhang, S., Liu, P., Zhang, H., Deng, H., Feng, K., et al. (2024) · Advanced Science · doi:10.1002/advs.202401127 · Cited by 6
Lai, Y., Liao, H.-T., Chen, Y., Huang, S., Liou, Y.-H., Wu, Z., & Liao, N. (2025) · Cancers · doi:10.3390/cancers17071130 · Cited by 5
“This is because tumor cells in advanced cancers have adapted to cope with the CIN-induced chronic activation of the cGAS–STING–IFN-I pathway by re-wiring the STING downstream signaling away from IFN-I induction so that IFN-I-mediated immune stimulation is lost [48,49].”
Functions and mechanisms of eukaryotic RNA-guided programmed DNA elimination
Stefanov, B., & Nowacki, M. (2025) · Biochemical Society Transactions · doi:10.1042/bst20253006 · Cited by 6
“Perturbations impede the evolutionary fitness, through multimodal effects including cancer evolution [1,2], and cause resistance to cytotoxic immune responses [3], anti-cancer drugs [3], and development of metastasis [4].”
Lakbir, S., de Wit, R., de Bruijn, I., Kundra, R., Madupuri, R., Gao, J., Schultz, N. D., Meijer, G. A., Heringa, J., Fijneman, R. J. A., et al. (2025) · npj Precision Oncology · doi:10.1038/s41698-025-00922-9 · Cited by 8
“The high number of SVs may lead to the activation of the cGAS-STING pathway, facilitating migration, invasion, and metastasis 47,48 .”
Liang, Z., Xu, Y., & Li, C. (2025) · DNA repair · doi:10.1016/j.dnarep.2025.103874 · Cited by 5
Bonassi, S., & Fenech, M. F. (2021) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2021.108390 · Cited by 6
Type 2 Dendritic Cells Orchestrate a Local Immune Circuit to Confer Antimetastatic Immunity
Weizman, O.-E., Luyten, S., Krykbaeva, I., Song, E., Mao, T., Bosenberg, M., & Iwasaki, A. (2023) · The Journal of Immunology · doi:10.4049/jimmunol.2200697 · Cited by 5
“Because chromosomal instability and dysregulation of nucleic acids are hallmarks of metastatic disease progression (33, 34), we investigated whether sensing of nucleic acids is required to activate DC immune responses against pioneering metastatic cells in the lung.”
Chen, R., Liu, M., Jiang, Q., Meng, X., & Wei, J. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1121603 · Cited by 5
“As a result, the cGAS-STING signaling pathway may have important implications in limiting cancer immune escape and metastasis (32).”
BackgroundDressel, N., Natusch, L., Munz, C. M., Ramon, S. C., Morcos, M. N. F., Loff, A., Hiller, B., Haase, C., Schulze, L., Müller, P., et al. (2023) · Cancer Research · doi:10.1158/0008-5472.can-22-3860 · Cited by 5
Reece, A. S., & Hulse, G. K. (2023) · Gastroenterology Insights · doi:10.3390/gastroent14020016 · Cited by 5
Mechanisms of Immune Sensing of DNA Damage
Goddard, A. M., Cho, M.-G., Lerner, L. M., & Gupta, G. P. (2023) · Journal of Molecular Biology · doi:10.1016/j.jmb.2023.168424 · Cited by 8
Microglial inflammation in genome instability: A neurodegenerative perspective
Maliar, N. L., Talbot, E., Edwards, A. R., & Khoronenkova, S. V. (2024) · DNA repair · doi:10.1016/j.dnarep.2024.103634 · Cited by 6
Broken chromosomes heading into mitosis: More than one way to patch a flat tire
Messer, C. L., & Fox, D. T. (2024) · The Journal of Cell Biology · doi:10.1083/jcb.202401085 · Cited by 5
“Micronuclei also upregulate cyclic GMP-AMP synthase (cGAS), an immune regulator linked to tumorigenesis (MacKenzie et al., 2017; Liu et al., 2018; Bakhoum et al., 2018).”
BackgroundInsight into the dichotomous regulation of STING activation in immunotherapy
Hu, Z., Yang, Y. K., Fang, L., Zhou, J., & Zhang, H. (2021) · Immunopharmacology and Immunotoxicology · doi:10.1080/08923973.2021.1890118 · Cited by 5
Errazquin, R., Sieiro, E., Moreno‐Sanchez, P. M., Ramı́rez, M. J., Lorz, C., Peral, J., Ortiz, J., Casado, J. A., Roman‐Rodriguez, F. J., Hanenberg, H., et al. (2021) · Genes · doi:10.3390/genes12040548 · Cited by 4
“This result is in line with reports indicating that HNSCC with DNA repair defects display features of invasive disease (Bakhoum et al., 2018, Bhide et al., 2016, Essers et al., 2019).”
ResultFu, X., Lei, H., Tao, Y., et al. (2021) · Journal of Computational Biology · doi:10.1089/cmb.2021.0255 · Cited by 5
“Copy number alterations (CNAs), which play a particularly vital role in how tumors adapt functionally over progression, are a common outcome of chromosome instability (CIN) (Heng et al., 2013; Bakhoum et al., 2018).”
Guo, S., Li, T., Xu, D., Xu, J., Wang, H., Li, J., Bi, X., Cao, M., Xu, Z., Xia, Q., et al. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.843640 · Cited by 5
“, 2008), confers tumorigenesis, metastasis, drug resistance, and poor prognosis (Lee et al., 2011; Duijf and Benezra, 2013; Bakhoum and Cantley, 2018; Bakhoum et al., 2018).”
BackgroundLiu, N., Liu, G., Ma, Q., & Li, X. (2023) · IET Systems Biology · doi:10.1049/syb2.12064 · Cited by 5
“Evidence suggests that CIN is implicated in cancer onset, progression, and immunotherapy [8–10 , 25].”
Zhu, S., Jiang, L., Wang, L., Wang, L., Zhang, C., Ma, Y., & Huang, T. (2019) · Cancer Management and Research · doi:10.2147/cmar.s179467 · Cited by 5
Forging New Strategies in the Cure of Human Oligometastatic Cancer
Greco, C., & FUKS, Z. Y. (2020) · JAMA Oncology · doi:10.1001/jamaoncol.2020.0195 · Cited by 5
Thermodynamic energetics underlying genomic instability and whole-genome doubling in cancer
Remacle, F., Graeber, T. G., & Levine, R. D. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1920870117 · Cited by 5
Harnessing tumor immune ecosystem dynamics to personalize radiotherapyPreprint
Grass, G. D., Alfonso, J. C. L., Welsh, E. A., Ahmed, K. A., Teer, J. K., Harrison, L. B., Cleveland, J. L., Mulé, J. J., Eschrich, S. A., Enderling, H., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.02.11.944512 · Cited by 5
Cheradame, L., Guerrera, I. C., Gaston, J., Schmitt, A., Jung, V. A., Pouillard, M., Radosevic‐Robin, N., Modesti, M., Judde, J., Cairo, S., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.07.11.196790 · Cited by 5
Monosomies, trisomies and segmental aneuploidies differentially affect chromosomal stabilityPreprint
Hintzen, D. C., Soto, M., Schubert, M., Bakker, B., Spierings, D. C. J., Szuhai, K., Lansdorp, P. M., Foijer, F., Medema, R. H., & Raaijmakers, J. A. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.08.31.458318 · Cited by 5
“Moreover, several studies have demonstrated that ongoing segregation errors in tumors are associated with enhanced therapy resistance, poor prognosis, and metastasis, thus reflecting adaptation conferred by CIN (Bakhoum et al., 2018; Swanton et al., 2009).”
BackgroundmicronuclAI: Automated quantification of micronuclei for assessment of chromosomal instabilityPreprint
Ibarra-Arellano, M. A., Caprio, L., Hada, A., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.05.24.595722 · Cited by 5
Amoeboid–mesenchymal transition and the proteolytic control of cancer invasion plasticity
Olson, A. W., Li, J., Li, X.-Y., King, L., Jiang, L., Banerjee, K., McCoy, A. J., Gondal, M. N., Chinnaiyan, A. M., El‐Ashry, D., et al. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2520717123 · Cited by 5
Costamagna, A., Noemi, G., & Martini, M. (2025) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2025.1726581 · Cited by 7
Extrachromosomal DNA and cancer: function, formation, and clinical implications
Wu, Y., Rui, R., Tian, T., et al. (2026) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-026-03639-0 · Cited by 4
“These conditions increase the frequency of chromosome segregation errors during mitosis, which in turn leads to sustained karyotypic reorganization-a hallmark of chromosomal instability (CIN) [25, 26].”
Gao, L., Wang, B., Liu, H., Liu, P., Liu, L., Han, J., Wang, X., Dou, B., Sun, F., Liu, W., et al. (2026) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2025-013247 · Cited by 6
“By demonstrating that PKMYT1 inhibition activates cGAS-STING signaling and enhances PD-L1 blockade efficacy, we provide a strong rationale for clinically evaluating this combination in PKMYT1-overexpressing patients with CRPC.”
Xia, Y., Hu, L., Hu, Y., Wang, S., Xiong, Q., Wang, X., Li, Y., Yin, L., Wang, J., & Li, S. (2026) · Journal of Controlled Release · doi:10.1016/j.jconrel.2026.114731 · Cited by 6
cGAS-STING pathway in lung cancer and emerging therapeutic approaches
Joshi, A., & Izgü, E. Ç. (2026) · Drug Discovery Today · doi:10.1016/j.drudis.2026.104646 · Cited by 5
STING-Activating Nanomedicines in Cancer Immunotherapy: Mechanisms, Design, and Therapeutic Outcomes
Singhai, H., Rehman, U., Bukhary, D. M., Gupta, G., Patil, U. K., Sahebkar, A., & Kesharwani, P. (2026) · International Immunopharmacology · doi:10.1016/j.intimp.2026.116692 · Cited by 5
The cGAS–STING pathway in cancer immunotherapy: prognostic value and therapeutic potential
Alabi, F. A., Imodoye, S. O., Adedokun, K. A., Eltokhy, M. A., Curcic, M., Okoyeocha, E., Thapa, I., Tiwari, S., Ogundele, A. V., Ayo, T. E., et al. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1760947 · Cited by 5
“These includes the natural genomic instability of tumor cells, oxidative stress, radiation, and chemotherapy-induced DNA damage and replication, if DNA leaks into the cytoplasm (18, 19).”
InfluentialTherapeutic targeting of the cGAS-STING pathway in human disease
Mahajan, A. S., Forsyth, C. M., Phung, C. D., Shen, X., Jarvis, R., & Stegh, A. H. (2026) · Journal of Clinical Investigation · doi:10.1172/jci204547 · Cited by 4
Targeting mitotic regulators in cancer as a strategy to enhance immune recognition
Gregorczyk, M., & Parkes, E. E. (2023) · DNA repair · doi:10.1016/j.dnarep.2023.103583 · Cited by 4
Jiang, C., & Wu, J. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1412296 · Cited by 4
Tay, J. Y., Ho, J., Cheo, F. F., & Iqbal, J. (2024) · Cancers · doi:10.3390/cancers16233910 · Cited by 5
Kannen, V., Rasmussen, M., Das, S., Giuliana, P., Izzati, F. N., Choksi, H., Erlingsson, L. A. M., Olafsen, N. E., Åhrling, S. S., Cappello, P., et al. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1513595 · Cited by 5
“STING activation in tumour cells has been reported to induce epithelial-mesenchymal transition (EMT) and promote tumour metastasis (21).”
Xu, F., Yu, D., Guo, J., Hu, J., Zhao, Y., Jiang, C., Meng, X., Cai, J., & Zhao, Y. (2025) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2025.108537 · Cited by 4
Chen, Z., Zhao, J., Li, Y., Feng, X., Chen, Y., Li, Y., Nan, X., Li, H., Dong, B., Shen, L., et al. (2025) · Gastric Cancer · doi:10.1007/s10120-025-01628-4 · Cited by 4
Fontana, A., Barbano, R., Pasculli, B., Mazza, T., Palumbo, O., Binda, E., Trivieri, N., Mencarelli, G., Laurenzana, I., Lamorte, D., et al. (2025) · Breast Cancer Research · doi:10.1186/s13058-025-02124-4 · Cited by 4
“In addition, both miR-3613-5p and miR-3916 are involved in DNA repair pathways, and genomic instability has been associated with early events in metastasis formation [33].”
RCC1 depletion drives protein transport defects and rupture in micronuclei
Zych, M. G., Contreras, M., Vashisth, M., Mammel, A., Ha, G., & Hatch, E. M. (2026) · The Journal of Cell Biology · doi:10.1083/jcb.202510133 · Cited by 4
LncRNAs-associated to genomic instability: A barrier to cancer therapy effectiveness
Andonegui-Elguera, M. A., Cáceres-Gutiérrez, R. E., Oliva-Rico, D., Díaz‐Chávez, J., & Herrera, L. A. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.984329 · Cited by 4
“Demonstrating that chromosomal instability promotes the invasive and metastatic phenotype (Bakhoum et al., 2018).”
BackgroundUnjamming tumour cell invasion through cGAS–STING
Deyell, M., & Bakhoum, S. F. W. (2023) · Nature Materials · doi:10.1038/s41563-023-01542-z · Cited by 4
Self-citationFeedback activation of CD73-Adenosine axis attenuates the antitumor immunity of STING pathway
Fu, N., Zhang, Z., & Quan, J. (2024) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2024.149814 · Cited by 5
Emerging role and function of SPDL1 in human health and diseases
Feng, Y., Tang, D., & Wang, J. (2024) · Open Medicine · doi:10.1515/med-2024-0922 · Cited by 4
“Defects in these three closely linked processes in the cell cycle, which are also the major sources of GIN, are related to tumor metastasis [49]. hSpindly participates in mitosis in tumors and in the chromosome segregation process, impel-ling GIN.”
BackgroundLi, W.-H., Lan, J., Zhou, C., Yang, R., Wang, J., He, J.-H., Xiao, B.-Y., Ou, Q.-J., Fang, Y.-J., Fan, W., et al. (2024) · Annals medicus · doi:10.1080/07853890.2024.2396559 · Cited by 3
“…of micronuclei whose rupture spills genomic DNa into the cytosol and then leads to the activation of the cGas-stiNG cytosolic DNa-sensing pathway [23]. interleukin-6 (il-6) – il-6R – stat3 signalling induced by cGas and stiNG is required for survival of ciN cancer cells [24]. il-6 was found to…”
Aberrant nuclei with amplified DNA in cancer
Kadali, V. N., & Shoshani, O. (2024) · Trends in cancer · doi:10.1016/j.trecan.2024.09.005 · Cited by 4
Hawillo, K., Kemiha, S., & Técher, H. (2024) · Onco · doi:10.3390/onco4040022 · Cited by 4
Ayala, C. I., Sathe, A., Bai, X., et al. (2025) · Frontiers in Genetics · doi:10.3389/fgene.2025.1536982 · Cited by 4
“Chromosomal instability (CIN) is a driver of metastasis (Bakhoum et al., 2018).”
The Winds of Change: Emerging Therapeutics in Prostate Cancer
Pezaro, C. J., Marciscano, A. E. E., & Madan, R. A. (2018) · American Society of Clinical Oncology Educational Book · doi:10.1200/edbk_201295 · Cited by 4
A comprehensive review on chemistry and pharmacology of marine bioactives as antimetastatic agents
Bhardwaj, N., Goel, B., Tripathi, N., Sahu, B. L., & Jain, S. K. (2021) · European Journal of Medicinal Chemistry Reports · doi:10.1016/j.ejmcr.2021.100023 · Cited by 7
Frequent Spindle Assembly Errors Require Structural Rearrangement to Complete Meiosis in Zea mays
Weiss, J. D., McVey, S. L., Stinebaugh, S. E., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23084293 · Cited by 4
“Mistakes in this process lead to aneuploidy [1], which is associated with tumorigenesis and metastasis in mitotic cells [2,3].”
BackgroundBiochemical, genomic, and epigenomic profiling of isolated cancer cell lines’ micronuclei
Agustinus, A. S., & Bakhoum, S. F. W. (2022) · Methods in cell biology · doi:10.1016/bs.mcb.2022.07.001 · Cited by 4
Self-citationBibliometric and Visualized Analysis of the Current Status on STING Signaling Pathway and Cancer
Lu, Z., Fu, Q., Sui, J., Chang, Y., Jin, T., & Zhang, M. (2022) · Journal of Oncology · doi:10.1155/2022/5095176 · Cited by 4
“Chromosomal instability (CIN) is a hallmark of cancer caused by ongoing errors in chromosome segregation during mitosis [10].”
BackgroundThe Link Between Chromosomal Instability and Immunity in Cancer
Kumari, L., Kumar, Y., & Bhatia, A. (2022) · Springer eBooks · doi:10.1007/978-3-030-80962-1_51-1 · Cited by 4
Advances in Radiotherapy Immune Modulation
Wang, C. X., Hunt, J., Feinstein, S., Kim, S. K., & Monjazeb, A. M. (2023) · Surgical Oncology Clinics of North America · doi:10.1016/j.soc.2023.02.009 · Cited by 4
Harnessing the cooperation between DNA‐PK and cGAS in cancer therapies
Taffoni, C., Schüssler, M., Vila, I. K., & Laguette, N. (2023) · BioEssays · doi:10.1002/bies.202300045 · Cited by 4
“cGAS-STING pathway activation in chromosomally unstable cancer cells induces NF-κB activation and thus tumour supporting inflammatory cytokine production,[53,54] ultimately promoting metastatic dissemination[32,54] and chemoresistance.”
BackgroundLiu, L., Wang, Y., Chang, J., Zhang, P., Xiong, S., & Liu, H. (2023) · iScience · doi:10.1016/j.isci.2023.106874 · Cited by 4
“The CIN is the main driver of tumor evolution and can promote cancer metastasis by maintaining the autonomous response of tumor cells to cytoplasmic DNA.”
BackgroundStrategies for the Management of Patients with Pancreatic Cancer with PARP Inhibitors
Golan, T., Raitses‐Gurevich, M., Beller, T., Carroll, J. R., & Brody, J. R. (2023) · Cancer treatment and research · doi:10.1007/978-3-031-30065-3_8 · Cited by 4
Molina, Ò., Ortega-Sabater, C., Thampi, N., Fernández‐Fuentes, N., Guerrero-Murillo, M., Martínez-Moreno, A., Vinyoles, M., Velasco-Hernández, T., Bueno, C., Trincado, J. L., et al. (2023) · EMBO Molecular Medicine · doi:10.1038/s44321-023-00006-w · Cited by 4
“CIN has been associated with tumor progression across different cancer types (Bakhoum et al, 2018; Foijer et al, 2014; Godek et al, 2016; Hoevenaar et al, 2020; van Dijk et al, 2021).”
Background
Metadata
- Authors
- Bakhoum, S. F., Ngo, B., Laughney, A. M., Cavallo, J.-A., Murphy, C. J., Ly, P., Shah, P., Sriram, R. K., Watkins, T. B. K., Taunk, N. K., Duran, M., Pauli, C., Shaw, C., Chadalavada, K., Rajasekhar, V. K., Genovese, G., Venkatesan, S., Birkbak, N. J., McGranahan, N., Lundquist, M., LaPlant, Q., Healey, J. H., Elemento, O., Chung, C. H., Lee, N. Y., Imielenski, M., Nanjangud, G., Pe’er, D., Cleveland, D. W., Powell, S. N., Lammerding, J., Swanton, C., & Cantley, L. C.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Weill Cornell Medicine (US)
- University of California San Diego (US)
- Cornell University (US)
- The Francis Crick Institute (GB)
- University Hospital Zurich (CH)
- Broad Institute (US)
- University College London (GB)
- Moffitt Cancer Center (US)
- Corresponding author
- Cantley, Lewis C.
- ORCID
- Bakhoum, Samuel F.
- Ngo, Bryan
- Laughney, Ashley M.
- Murphy, Charles J.
- Ly, Peter
- Shah, Pragya
- Watkins, Thomas B. K.
- Taunk, Neil K.
- Pauli, Chantal
- Chadalavada, Kalyani
- Rajasekhar, Vinagolu K.
- Genovese, Giulio
- Venkatesan, Subramanian
- Birkbak, Nicolai J.
- McGranahan, Nicholas
- Lundquist, Mark
- LaPlant, Quincey
- Healey, John H.
- Elemento, Olivier
- Chung, Christine H.
- Lee, Nancy Y.
- Nanjangud, Gouri
- Pe’er, Dana
- Cleveland, Don W.
- Powell, Simon N.
- Lammerding, Jan
- Swanton, Charles
- Cantley, Lewis C.
- Venue
- Nature
- Published
- 2018-01-17
- Volume
- 553
- Issue
- 7689
- Pages
- 467-472
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5785464
- OpenAlex
- W2783667606
- Cited by
- 1,593
- References
- 59
- Citations by year
- 2026: 215 · 2025: 213 · 2024: 223 · 2023: 216 · 2022: 190 · 2021: 203 · 2020: 149 · 2019: 105 · 2018: 76
- FWCI
- 55.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Science Foundation (1254846, CA008748, 1257284)
- Breast Cancer Research Foundation (CA008748)
- Elsa U. Pardee Foundation
- Memorial Sloan-Kettering Cancer Center (CA008748, P30 CA008748)
- Johns Hopkins University
- Francis Crick Institute (10169)
- Gray Foundation
- Cancer Research UK (20466, 19310, 17786)
- Rosetrees Trust (M231-CD1)
- National Institutes of Health (NIH-R01, W81XWH)
- Medical Research Council (MR/P014712/1)
- National Heart, Lung, and Blood Institute (R01HL082792)
- National Cancer Institute (R01CA169306, U54CA210184, R01CA187069, K99CA218871, P30CA008748, R35CA197588)
- National Institute of General Medical Sciences (R35GM122476)
- Division of Chemical, Bioengineering, Environmental, and Transport Systems (CBET-1254846)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- chromosomal instability, metastasis, cytosolic DNA sensing, cGAS-STING pathway, micronuclei, chromosome segregation errors, NF-κB signaling, innate immunity, tumor inflammation, aneuploidy, tumor invasion
- MeSH terms
- STING Protein, Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase, Animals, Brain Neoplasms, Breast Neoplasms, Carcinoma, Squamous Cell, Cell Line, Cytosol, DNA, Neoplasm, Female, Head and Neck Neoplasms, Humans, Inflammation, Membrane Proteins, Mesoderm, Neoplasm Metastasis, Nucleotidyltransferases, NF-kappa B, Chromosome Segregation, Xenograft Model Antitumor Assays, Chromosomal Instability, Micronuclei, Chromosome-Defective, Mice
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 2026-10-19, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-19 (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.
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
