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.
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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.
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- Based: passes — The paper gives a reason why it holds.
- Supported
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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.
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- 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.
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- 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.
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- 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.
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- 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.
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- 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.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- 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.
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- 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.
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- 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.
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- 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.
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- 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.
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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.
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- 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.
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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.
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- 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
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STAR: ultrafast universal RNA-seq aligner
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HTSeq—a Python framework to work with high-throughput sequencing data
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Massively parallel digital transcriptional profiling of single cells
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Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway
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circlize implements and enhances circular visualization in R
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Nextflow enables reproducible computational workflows
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Cited by
Sorted by citations
Items 1,501–1,551 of 1,551
MCT4-mediated lactate efflux promotes STING-dependent dendritic cell antitumor immunity
Ding, R., Yuan, Y., Xu, T., Zhang, J., Zhu, Y., Yao, B., Qu, S., & Hu, Z. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.117778
The cGAS/STING pathway in cancer: translating innate DNA sensing into therapeutic potential
Wang, Y., Angulo-Lozano, J. C., Wang, Y., & Deng, L. (2026) · Journal of Clinical Investigation · doi:10.1172/jci204552 · Cited by 2
A molecular glue induces aberrant STING oligomerization and inhibits autoinflammatory diseases
Zi-wen, F., Zeng, T., Shu, Q., Li, X.-Z., Yu, H., Dai, W., Liu, X., Tian, X.-J., Xu, F., Li, H., et al. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-026-02863-6
Li, J., Wang, L., Mao, X., Hu, D., Lu, Q., Shi, C., Wang, Y., Meng, Z., Fan, H., & Sun, H. (2026) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.6c00132
Beyond Structure: The Dynamic Role of the Extracellular Matrix Components in Immune Evasion
Maqbool, M., Surendranath, A., Baba, S. K., Jawwad, T., Elfaki, I., Mir, R., Kumar, R., Shahab Uddin, M. S., Haris, M., Macha, M. A., et al. (2026) · 癌症：英文版 · doi:10.34133/cancomm.0045
Egan, D., Shum, B., Fidan, R., Kolch, W., Brennan, D. J., Lobón, I., & Turajlic, S. (2026) · Cell Reports Medicine · doi:10.1016/j.xcrm.2026.102981
“43 Gene fusion burden demonstrated a near-significant increase in primary resistance versus AR patients ( p = 0.055) (Figure 5E).”
InfluentialCHD4 and CENPE contribute to the maintenance of mitotic progression in T-ALL
Weng, C., Sun, T., Huang, H., & Lu, C. (2026) · Gene Reports · doi:10.1016/j.genrep.2026.102603
Zhan, C., Zhai, Y., Chen, T., Shen, X., Wang, Z., Ma, S., & Chen, S. (2026) · Cancers · doi:10.3390/cancers18162594
“Along with reports that autonomous STING signaling in tumor cells drives malignant progression [27,28], we proposed that internalized necrotic mtDNA in residual tumor cells after iMWA may promote a malignant phenotype through tumor-intrinsic STING signaling.”
Clinical metastatic cancer from initiation to colonization: emerging challenges and breakthroughs
Niu, G., & Hagerling, C. (2026) · Oncogene · doi:10.1038/s41388-026-03944-0
Wang, Y., Wang, L., Deng, J., Tian, Z., Liang, Z., & Zhang, H. (2026) · Experimental Cell Research · doi:10.1016/j.yexcr.2026.115150
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Lipidation as a Driver of Spatial Organization and Function in Proteins and Nucleic Acids
Zhang, H., & Izgü, E. Ç. (2026) · ACS Chemical Biology · doi:10.1021/acschembio.6c00528
EWSR1::FLI1 promotes neocentromere formation in ewing sarcoma cells
Kitagawa, R., Metitiri, E. E., Yu, B., Shen, C., Bishop, A. J. R., Zheng, S., Houghton, P. J., & Kitagawa, K. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.117846
Atomic‐Level Strain‐Engineered Piezoelectric Nanosheets for cGAS‐STING Activation
Yang, L., Zang, P., Zhang, R., Yang, M., Yu, C., Yang, M., Tian, B., Yao, Y., Gai, S., & Yang, P. (2026) · Angewandte Chemie International Edition · doi:10.1002/anie.5643285
Atomic‐Level Strain‐Engineered Piezoelectric Nanosheets for cGAS‐STING Activation
Lü, Y., Zang, P., Zhang, R., Yang, M., Yu, C., Yang, M., Tian, B., Yao, Y., Gai, S., & Yang, P. (2026) · Angewandte Chemie · doi:10.1002/ange.5643285
Pan, Y., Zhou, Y., Deng, J., Liu, F., & Lei, G. (2026) · iMetaMed · doi:10.1002/imm3.70056
Hadi, J. A., Nizami, Z. N., Noor, A. T., Osman, A. A., & Myers, J. N. (2026) · Cancers · doi:10.3390/cancers18172724
“…can paradoxically promote tumor progression: chromosomal instability-driven, sustained cGAS-STING signaling has been shown to drive a pro-metastatic tumor microenvironment through non-canonical NF-κ B signaling and type I interferon tachyphylaxis, rather than durable antitumor immunity [143].”
Ali, W., Mamun, M. A. A., He, Y., et al. (2026) · Future Journal of Pharmaceutical Sciences · doi:10.1186/s43094-026-01017-3
“Although this pathway initially enhances antitumor immunity, chronic activation has been shown to recruit immunosuppressive myeloid cells, thereby fostering tumor progression [83, 84].”
Stress-driven strategic games in cancer
Özcan, S. C. (2026) · Biosystems · doi:10.1016/j.biosystems.2026.105929
The cGAS-STING/MITA pathway in innate antiviral immunity and beyond
Li, F.-X., & Zhong, B. (2026) · Cell Insight · doi:10.1016/j.cellin.2026.100357 · Cited by 1
“…hypermethylation of the STING1 promoter and its 3 ′ enhancer elements or TGF-β -driven repressive chromatin modifications or through selective degradation pathways, thereby attenuating STING availability and signaling (Bakhoum et al., 2018; Konno, Yamauchi, et al., 2018; Xia, Konno, et al., 2016).”
Wang, B., Yao, L., Zhao, Y., Su, Z., Chen, J., You, T., Wu, L., Wang, L., Wang, W., Liu, G., et al. (2026) · Research Square · doi:10.21203/rs.3.rs-10456885/v1
Wang, Y., Boev, N. B., García‐Lepe, U. O., MacDonald, K. M., Harding, S. M., & Kumar, S. (2026) · Cell Reports Methods · doi:10.1016/j.crmeth.2026.101573
Zou, Z., Liu, H., Hu, Y., Ge, X., Zhang, J., & Li, X. (2026) · Frontiers in Microbiology · doi:10.3389/fmicb.2026.1923929
“Persistent mitochondrial dysfunction further maintains elevated reactive oxygen species (ROS) production, converting the transient physicochemical radiation insult into chronic oxidative stress (Jackson and Bartek, 2009; Zhao and Robbins, 2009; Rong et al., 2025; Bakhoum et al., 2018).”
Remodeling of innate antiviral immunity in aging
Zhang, X., & Yang, Q. (2026) · Cell Insight · doi:10.1016/j.cellin.2026.100362
“In contrast, chronic tumor-cell-intrinsic cGAS-MITA/STING activation caused by chromosomal instability or micronuclear DNA leakage can activate noncanonical NF-κ B programs and has been linked to invasion, metastasis, or therapy resistance in some contexts (Bakhoum et al., 2018).”
Bioceramic bone tissue-engineered substitutes with anti-inflammatory effects in periodontitis
Xiao, B.-Y., Han, Y.-Z., Wei, C.-Q., Pei, Y.-F., Wu, Y.-X., Wang, Z.-B., Wang, H.-C., & Zhou, Y.-M. (2026) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2026.1934456
“For example, cGAS-STING stimulation also promotes inflammation by triggering p52-RELB nuclear translocation to promote a nonclassical NF-κ B response (Bakhoum et al., 2018; Hou et al., 2018).”
Context-Dependent cGAS-STING Activation Shapes Metastatic Progression and Dormancy
Akter-Yasuoka, E., 이탁, Murayama, T., & Nakayama, J. (2026) · Cells · doi:10.3390/cells15171619
“…reported that cytoplasmic DNA derived from unstable chromatin activates noncanonical NF-kB in a STING-dependent, but TBK-1-independent manner, thereby promoting metastasis of breast cancer cells [62], further indicating that cGAS-STING activation in cancer cells can be sometimes tumor-promoting.”
Xiang, S., Ma, S., Xu, T., Yu, W., Wang, J., You, X., Chai, M., Wang, X., Wang, X., Zhang, J., et al. (2026) · Cell Reports Medicine · doi:10.1016/j.xcrm.2026.103025
Modeling meningioma in vitro in the omics era
Sato, D., Miyawaki, S., Sakai, Y., Kitagawa, Y., Hongo, H., Hirano, Y., Teranishi, Y., Ogawa, S., Tsuchiya, T., Hirata, S., et al. (2026) · Human Cell · doi:10.1007/s13577-026-01448-3
“Since then, numerous mechanistic studies, many of them centered on cell line models, have investigated how aneuploidy arises and reshapes tumor evolution [130–133].”
STING signaling in liver diseases and the therapeutic potential of nanodrug delivery systems
Nie, S., Qian, X., Zhao, Y., Yao, T., Munyonyela, W. W., Zhang, H., Hu, M., Wu, S., Wu, G., Chen, P., et al. (2026) · Genes & Diseases · doi:10.1016/j.gendis.2026.102453
Synthetic Lethality in Cancer Therapy
Nune, S. S., & Halder, S. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-24738-5.00107-5
Chen, G., Hu, M., Li, Z., Yang, K., Chen, B., & Xu, T. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1837053
“…rupture releases genomic DNA into the cytosol and activates cyclic GMP-AMP synthase (cGAS) – stimulator of interferon genes (STING) signaling; in the same study, however, continuous segregation errors promoted invasion and metastasis in a STING-dependent manner rather than immune clearance (57).”
Djabali, K. (2026) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2026.112255
Chromosomal instability in cancer: sources, consequences and new therapeutic opportunities
Serpico, A. F., & Grieco, D. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-026-02940-w
“199 ,276,295 In addition, cGAS can exert homeostatic functions by limiting excessive CIN through MN autophagy.”
InfluentialYang, Y., Yin, Y., Rong, S., Qian, Y., Li, D., Zhang, Y., & Wang, X. (2026) · Cancer and Metastasis Reviews · doi:10.1007/s10555-026-10380-9
Radiation-induced cell-death states in cancer: Toward biomarker-guided radioimmunotherapy
Wang, X., (2085), W. G., Wang, Q., He, S., & Zou, B. (2026) · Cancer Letters · doi:10.1016/j.canlet.2026.218860
The role of organelles as mechanotransducers
Rawal, S., Marwaha, R., & Das, T. (2026) · FEBS Journal · doi:10.1111/febs.70739
Genomic correlates of metastatic competence and progression in human melanomaPreprint
Chatziioannou, E., Luthria, K. D., Shah, P., Armeanu–Ebinger, S., Admard, J., Schroeder, C., Forchhammer, S., Stihler, F., Zhang, X., Maiche, S., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.09.23.753695
“While CIN is now a well-established hallmark of metastatic lesions in melanoma and other cancers 13,14,22,25,28,38 little is known about how CIN in primary tumours dictates metastasis risk and progresses in matched lesions.”
Self-citationBılır, A., Yıldırım, B., & Karalök, M. H. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27198775
“Persistent chromosomal instability and chronic cytosolic DNA signaling can promote tumor evolution, inflammatory adaptation, and metastasis [48,56].”
InfluentialLiu, F., Ma, X., Guan, Y., Jia, M., Yang, Z., Feng, X., Xin, M., & Liu, G. (2026) · Research Square · doi:10.21203/rs.3.rs-11096418/v1
Immunologic Consequences of Genomic Instabilities
Alouani, E. L., Fumet, J.-D., Johannet, P. M., Marabelle, A., & Rousseau, B. (2026) · Cancer Discovery · doi:10.1158/2159-8290.cd-25-2063
cGAS–STING and DNA Damage Repair
Patterson-Fortin, J. (2026) · IntechOpen eBooks · doi:10.5772/intechopen.1017633
Tu, Y., Xu, L., Tian, C., 石, 沅., Yu, J., Gong, C., Peng, T., Yu, H., Yuan, R., & Jiang, P. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1905624
Patrad, E., & Alizadeh, A. M. (2026) · Experimental and Molecular Pathology · doi:10.1016/j.yexmp.2026.105083
Wang, S., Chen, P., Jing, X., Zou, J., Li, L., Jiang, C., Qian, N., Zhang, X., Shi, L., Xu, Y., et al. (2026) · Materials & Design · doi:10.1016/j.matdes.2026.117182
AI‐Assisted Micronucleus Detection: A Critical Systematic Review With Quantitative Synthesis
Paul, S. (2026) · Cell Biology International · doi:10.1002/cbin.70225
“Furthermore, chromosomal instability perpetuates this cytosolic DNA response and promotes metastasis, positioning MN as functional intermediates in genome evolution and inflammatory signaling (Bakhoum et al. 2018).”
Extrachromosomal DNA: A New Therapeutic Frontier for Overcoming Cancer Drug Resistance
Jeoung, D. (2026) · Cells · doi:10.3390/cells15201834
“These structures can be fragile and undergo membrane rupture, which exposes the ecDNA to cytosolic DNA sensors such as cyclic GMP–AMP synthase (cGAS) (Figure 5C) [106–108].”
Liu, B., Zang, J., Guo, L., Wang, F., Cui, X., & 石栋 (2026) · Comprehensive physiology · doi:10.1002/cph4.70260
Escape from replicative crisis and immortalization precedes complex genome evolutionPreprint
Schmidt, T. T., Cosenza, M. R., Popay, T. M., Przetocka, S., Haggblom, C., Allsing, N., Lande, K., Grimstead, J. W., Williams, A. E., Baird, D. A., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.09.758087
Morales-Hernández, A., Tirado-Garibay, A. C., Ochoa‐Zarzosa, A., et al. (2026) · Scientia Pharmaceutica · doi:10.3390/scipharm94040095
Beyond PD-L1 and HER2: emerging predictive biomarkers in gastroesophageal tumors
Alsina, M., Terán, E., & Fleitas, T. (2026) · ESMO Gastrointestinal Oncology · doi:10.1016/j.esmogo.2026.100430
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.
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