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
24 of 29 cited sources checked · 10 supported · 0 flagged · 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)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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)
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- 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)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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)
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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)
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- 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)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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)
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
Load-bearingStrength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably 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
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Strength:plain· not yet calibratedn = 3Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably 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
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Strength:hedged· not yet calibratedn = 10Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Strength:hedged· not yet calibratedn = 10Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Noncanonical NF-κB protein ratios differ between the text and figure caption
MinorThe text describes ratios of p52 and phosphorylated p100 to total p100. The Extended Data Figure 8 caption instead names phosphorylated p52-to-p100 and p100-to-total p100 ratios.
“a trend toward higher ratios of p52 and phosphorylated p100 relative to total p100”
“Normalized ratio of phosphorylated p52-to-p100 (left) and p100-to-total p100 (right) protein levels.”
PCR indexing step is described as both 10 and 14 cycles
MinorThe methods give two different cycle counts for the same sample-index PCR amplification.
“A unique sample index for each library was introduced through 10 cycles of PCR amplification”
“(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
Flagged first, then by citations
Cited by
Sorted by citations
Items 401–500 of 1,551
Ye, C. J., Sharpe, Z. J., & Heng, H. H. (2020) · Genes · doi:10.3390/genes11101162 · Cited by 42
“Recent work has shown a critical link between micronuclei formation and massive genome rearrangements [29], along with cancer progression and metastasis [71].”
BackgroundAntimetastatic Effects of Curcumin in Oral and Gastrointestinal Cancers
Davoodvandi, A., Farshadi, M., Zare, N., Akhlagh, S. A., Nosrani, E. A., Mahjoubin‐Tehran, M., Kangari, P., Sharafi, S. M., Khan, H. Z., Aschner, M., et al. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.668567 · Cited by 44
“It functions as a cytosolic DNAsensing pathways activator (cyclic GMP-AMP synthase–stimulator of interferon (IFN) genes) and finally activation of nuclear factor ?-light-chain-enhancer B (NF-κB) signaling pathway (Bakhoum et al., 2018).”
BackgroundChromosomal instability and its effect on cell lines
He, Z., Wilson, A., Rich, F. J., Kenwright, D., Stevens, A. J., Low, Y. S., & Thunders, M. C. (2023) · Cancer Reports · doi:10.1002/cnr2.1822 · Cited by 47
“Chronic activation of the cGAS-STING pathway promotes cancer invasion and metastasis through STING and downstream noncanonical NF-κB pathway.(18) Another consequence of CIN is the formation of extrachromosomal DNA (ecDNA) hubs, which can lead to the rapid malignant transformation of cells.”
BackgroundBeyond DNA sensing: expanding the role of cGAS/STING in immunity and diseases
Seok, J. K., Kim, M., Kang, H. C., Cho, Y., Lee, H. S., & Lee, J. Y. (2023) · Archives of Pharmacal Research · doi:10.1007/s12272-023-01452-3 · Cited by 45
Wang, M., Zhao, Y., Liu, J., Fan, R., Tang, Y., Guo, Z., & Li, T. (2024) · Acta Pharmacologica Sinica · doi:10.1038/s41401-023-01185-5 · Cited by 42
“Therefore, restoration of the normal function of the cGAS-STING signaling pathway could serve as a promising therapeutic strategy for cancer treatment [86].”
DNA repair and the contribution to chemotherapy resistance
Nesic, K., Parker, P., Swisher, E. M., & Krais, J. J. (2025) · Genome Medicine · doi:10.1186/s13073-025-01488-8 · Cited by 57
“Pro-inflammatory signaling rapidly decreases with damage repair; however, chronic activation in some cancer settings can instead promote immune evasion, invasive phenotypes, and metastasis [338].”
Segura‐Bayona, S., Villamor-Payà, M., Attolini, C. S., König, L. M., Sanchiz-Calvo, M., Boulton, S. J., & Stracker, T. H. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107983 · Cited by 43
“However, IFN responses have also been implicated in promoting metastasis in CIN tumors, and it is likely that important context-dependent effects of agents that activate STING will need to be considered (Bakhoum et al., 2018).”
BackgroundImpact of cancer evolution on immune surveillance and checkpoint inhibitor response
Wu, Y., Biswas, D., & Swanton, C. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.02.013 · Cited by 43
Self-citationRidder, D. A., Weinmann, A., Schindeldecker, M., Urbansky, L. L., Berndt, K., Gerber, T. S., Lang, H., Lotz, J., Lackner, K. J., Roth, W., et al. (2021) · International Journal of Cancer · doi:10.1002/ijc.33898 · Cited by 42
“Chromosomal instability has recently been shown to drive metastasis and may explain the increased metastatic capacity of AFP-positive tumor cells.(45) Furthermore, we confirmed previously published results that AFP-positive HCCs showed increased expression of the hepatic progenitor cell marker CK19 and of the establis…”
ResultGenomic instability drives tumorigenesis and metastasis and its implications for cancer therapy
Guo, S., Zhu, X. M., Huang, Z., Wei, C., Yu, J., Zhang, L., Feng, J., Li, M., & Li, Z. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.114036 · Cited by 44
Therapy sculpts the complex interplay between cancer and the immune system during tumour evolution
Thol, K., Pawlik, P., & McGranahan, N. (2022) · Genome Medicine · doi:10.1186/s13073-022-01138-3 · Cited by 47
“Under normal conditions, cGAS-STING activates canonical NF-κB signalling and downstream type 1 interferon signalling; however, in cells with high CIN, non-canonical NF-κB signalling was shown to be activated, which decreased type 1 interferon signalling and increased metastasis [30].”
BackgroundSelf-citationInhibitory targeting cGAS-STING-TBK1 axis: Emerging strategies for autoimmune diseases therapy
Zhang, M., Zou, Y., Zhou, X., & Zhou, J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.954129 · Cited by 43
“The stimulation of cGAS-STING also promotes a non-canonical NF-kB response by triggering p52 nuclear translocation (Figure 4) (73, 74).”
BackgroundTaffoni, C., Marines, J., Chamma, H., Guha, S., Saccas, M., Bouzid, A., Valadão, A. L. C., Maghe, C., Jardine, J., Park, M. K., et al. (2022) · The EMBO Journal · doi:10.15252/embj.2022111961 · Cited by 43
“…the cGAS-STING axis has been shown to support the survival of chromosomally unstable cancers (Hong et al , 2022), providing an explanation for cGAS-STING inactivation in primary tumors (Bakhoum & Cantley, 2018, Bakhoum et al , 2018) and activation in late tumorigenesis (Mayca Pozo et al , 2021).”
BackgroundThe Force is Strong with This Epigenome: Chromatin Structure and Mechanobiology
Hsia, C.-R., Melters, D. P., & Dalal, Y. (2023) · Journal of Molecular Biology · doi:10.1016/j.jmb.2023.168019 · Cited by 40
Targeting chromosomal instability in patients with cancer
Al-Rawi, D. H., Lettera, E., Li, J., Bona, M. D., & Bakhoum, S. F. W. (2024) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-024-00923-w · Cited by 41
“…of chronic inflammatory signalling that stimulates cancer cell-intrinsic changes, such as epithelial-to-mesenchymal transition, as well as alterations in the tumour immune microenvironment culminating in immune suppression are important mechanisms through which CIN supports tumour progression 15 .”
InfluentialSelf-citationUrooj, T., Wasim, B., Mushtaq, S., Shah, S. N. N., & Shah, M. (2019) · Current Cancer Drug Targets · doi:10.2174/1568009620666191220151856 · Cited by 39
Development of small molecule inhibitors/agonists targeting STING for disease
Liu, K., Lan, Y., Li, X., Li, M., Cui, L., Luo, H., & Luo, L. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110945 · Cited by 42
Perillaldehyde Inhibition of cGAS Reduces dsDNA-Induced Interferon Response
Chu, L., Li, C., Li, Y., Yu, Q., Yu, H., Li, C., Meng, W., Zhu, J., Wang, Q., Wang, C., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.655637 · Cited by 39
“In chromosomal instability tumor cells, genomic DNA existed in cytoplasm activated cGAS-STING and downstream NF-kB signaling, promoting tumor cell invasion and metastasis (41).”
BackgroundSTINGing the Tumor Microenvironment to Promote Therapeutic Tertiary Lymphoid Structure Development
Filderman, J. N., Appleman, M., Chelvanambi, M., Taylor, J. L., & Storkus, W. J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.690105 · Cited by 42
Therapy Induced Genome Chaos: A Novel Mechanism of Rapid Cancer Drug Resistance
Ye, J. C., Horne, S. D., Zhang, J. Z., Jackson, L., & Heng, H. H. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.676344 · Cited by 39
“Sixth, metastasis is also being linked to chromosome-mediated macroevolution, supporting our prediction (Bloomfield and Duesberg, 2016; Gao et al., 2016; Bakhoum et al., 2018).”
ResultThe Replication Stress Response on a Narrow Path Between Genomic Instability and Inflammation
Técher, H., & Pasero, P. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.702584 · Cited by 37
Chromosomal Instability in Genome Evolution: From Cancer to Macroevolution
Comaills, V., & Castellano‐Pozo, M. (2023) · Biology · doi:10.3390/biology12050671 · Cited by 40
“Chromosomal instability is even enriched in metastases of several cancer types [81,82].”
BackgroundSenataxin and R-loops homeostasis: multifaced implications in carcinogenesis
Gatti, V., Domenico, S. D., Melino, G., & Peschiaroli, A. (2023) · Cell Death Discovery · doi:10.1038/s41420-023-01441-x · Cited by 38
“Indeed, several evidence indicates that this pathway may favor tumor metastasis and facilitate cancer progression [96, 97].”
BackgroundColangelo, N. W., Gerber, N. K., Vatner, R. E., & Cooper, B. T. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1383000 · Cited by 44
Mechanistic link between DNA damage sensing, repairing and signaling factors and immune signaling
Mukherjee, S., Abdisalaam, S., Bhattacharya, S., Kalayarasan, S., Sinha, D., & Asaithamby, A. (2019) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2018.11.004 · Cited by 39
“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript cancers (Bakhoum et al., 2018).”
BackgroundBehind the Wheel of Epithelial Plasticity in KRAS-Driven Cancers
Arner, E. N., Du, W., & Brekken, R. A. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.01049 · Cited by 40
“In human breast and lung cancerderived cell lines, chronic cGAS-STING activity resulting from chromosome instability has been shown to drive migration, invasion, and metastasis (140).”
BackgroundInfluentialEndomembranes promote chromosome missegregation by ensheathing misaligned chromosomes
Ferrándiz, N., Downie, L., Starling, G. P., & Royle, S. (2022) · The Journal of Cell Biology · doi:10.1083/jcb.202203021 · Cited by 35
Chromosomal instability as a source of genomic plasticity
Al-Rawi, D. H., & Bakhoum, S. F. W. (2022) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2022.101913 · Cited by 41
Self-citationThe Role of cGAS-STING in Age-Related Diseases from Mechanisms to Therapies
Zheng, W., Feng, D., Xiong, X., Liao, X., Wang, S., Xu, H., Le, W., Wei, Q., & Yang, L. (2023) · Aging and Disease · doi:10.14336/ad.2023.0117 · Cited by 39
“In contrast, the cGAS-STING pathway can also promote tumor proliferation and metastasis [117, 134].”
BackgroundLuo, T., Jiang, X., Fan, Y., Yuan, E., Li, J., Tillman, L., & Lin, W. (2024) · National Science Review · doi:10.1093/nsr/nwae167 · Cited by 39
“RT often induces an immunosuppressive TME due to increased recruitment of myeloid-derived suppressor cells (MDSCs), upregulation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κβ ) and exhaustion of lymphoid cells [14 ,15 ].”
BackgroundMonti, M., Ferrari, G., Gazzurelli, L., Bugatti, M., Facchetti, F., & Vermi, W. (2024) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-024-03121-9 · Cited by 44
“In the TME, cancer cells are well-known to be repleted with cytosolic dsDNA derived from the rupture of micro-nuclear envelopes [274, 275], intrinsic DNA damage or exogenous genomic stress [275–278].”
BackgroundAbove and Beyond Watson and Crick: Guanine Quadruplex Structures and Microbes
Seifert, H. S. (2018) · Annual Review of Microbiology · doi:10.1146/annurev-micro-090817-062629 · Cited by 38
Lama-Sherpa, T. D., & Shevde, L. A. (2019) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-19-0665 · Cited by 37
“cGAS–STING pathway activation also has a supporting role in tumor growth and metastasis (47, 55, 56).”
BackgroundJiang, B., Mu, Q., Qiu, F., Li, X., Xu, W., Yu, J., Fu, W., Cao, Y. B., & Wang, J. (2021) · Nature Communications · doi:10.1038/s41467-021-27017-w · Cited by 39
“The previous study has demonstrated that chromosomal instability, featured by high FGA, is a driver of metastasis through a cytosolic DNA response 25 .”
BackgroundResultThe clinical and molecular significance associated with STING signaling in breast cancer
Parkes, E. E., Humphries, M. P., Gilmore, E. S., Sidi, F. A., Bingham, V., Phyu, S. M., Craig, S. G., Graham, C., Miller, J. J., Griffin, D., et al. (2021) · npj Breast Cancer · doi:10.1038/s41523-021-00283-z · Cited by 37
Self-citationMYO10 drives genomic instability and inflammation in cancer
Pozo, F. M., Geng, X., Tamagno, I., Jackson, M. W., Heimsath, E. G., Hammer, J. A., Cheney, R. E., & Zhang, Y. (2021) · Science Advances · doi:10.1126/sciadv.abg6908 · Cited by 36
“Nevertheless, continuous activation of the cGAS/STING pathway driven by genomic instability has been reported to induce chronic inflammation, fueling cancer progression probably by suppressing cytotoxic T cells in the tumor microenvironment (12, 18).”
BackgroundLi, N., Zheng, X. Y., Chen, M., Huang, L., Chen, L., Huo, R., Li, X., Huang, Y., Sun, M., Mai, S., et al. (2022) · Clinical & Translational Immunology · doi:10.1002/cti2.1386 · Cited by 38
“of cGAS in cancer cells, instead of dendritic cells, could induce inflammation and tumor metastasis.(23,27,35) It was reported that chronic induction of nuclear DNA leakage into the cytosol activated STING-dependent cytokine production and tumorigenesis.”
BackgroundStrategies involving STING pathway activation for cancer immunotherapy: Mechanism and agonists
Pan, X., Zhang, W., Guo, H., Wang, L., Wu, H., Ding, L., & Yang, B. (2023) · Biochemical Pharmacology · doi:10.1016/j.bcp.2023.115596 · Cited by 36
Cytosolic nucleic acid sensing as driver of critical illness: mechanisms and advances in therapy
Chen, Z., Behrendt, R., Wild, L., Schlee, M., & Bode, C. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02174-2 · Cited by 44
Factors promoting nuclear envelope assembly independent of the canonical ESCRT pathway
Lee, I., Stokasimov, E., Dempsey, N. W. M., et al. (2020) · The Journal of Cell Biology · doi:10.1083/jcb.201908232 · Cited by 36
Defining Immunogenic and Radioimmunogenic Tumors
Medler, T. R., Blair, T. C., Crittenden, M. R., & Gough, M. J. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.667075 · Cited by 38
“Recently, chromosome unstable cancers were shown to accumulate micronuclei at a high rate, and these micronuclei activate cGAS-STING DNA sensing pathways (63).”
BackgroundEZH2–CCF–cGAS Axis Promotes Breast Cancer Metastasis
Duan, D., Shang, M., Han, Y., Liu, J., Liu, J., Kong, S. H., Hou, J., Huang, B., Lü, J., & Zhang, Y. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031788 · Cited by 37
“(mitotic centromere-associated kinesin) overexpression can decrease CIN, thereby reducing the cytoplasmic DNA levels, while dnMCAK (dominant-negative MCAK mutant) overexpression can increase CIN, further increasing cytoplasmic DNA levels [7].”
BackgroundInfluentialPersistent DNA damage associated with ATM kinase deficiency promotes microglial dysfunction
Bourseguin, J., Cheng, W., Talbot, E., Hardy, L., Lai, J. F., Jeffries, A. M., Lodato, M. A., Lee, E. A., & Khoronenkova, S. V. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac104 · Cited by 36
“B target genes previously identified in chromosomally unstable metastatic breast cancer cells (36).”
InfluentialSeo, J., Kim, H., Min, K. I., Kim, C., Kwon, Y., Zheng, Z., Kim, Y., Park, H., Ju, Y. S., Roh, M. R., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29925-x · Cited by 41
Deng, Z., Cui, L., Li, P., Ren, N., Zhong, Z., Tang, Z., Wang, L., Gong, J., Cheng, H., Guan, Y., et al. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-04223-4 · Cited by 35
Vicencio, J. M., Evans, R., Green, R., An, Z., Deng, J., Treacy, C. A., Mustapha, R., Monypenny, J., Costoya, C., Lawler, K., et al. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-04701-3 · Cited by 33
“The DNA sensor cGAS can be activated in a tumor-autonomous way by chromosomal instability leading to cancer-cell STING activation [61], but can also lead to cGAMP transfer to surrounding immune cells, activating STING in trans, leading to type-I IFN production in antigen presenting cells and importantly, in macrophage…”
BackgroundActivating the Nucleic Acid-Sensing Machinery for Anticancer Immunity
Medler, T. R., Patel, J. M., Alice, A. F., Baird, J. R., Hu, H., & Gough, M. J. (2018) · International review of cytology · doi:10.1016/bs.ircmb.2018.08.006 · Cited by 36
Pawlikowska, P., Faugeroux, V., Oulhen, M., Aberlenc, A., Tayoun, T., Pailler, E., & Farace, F. (2019) · Journal of Thoracic Disease · doi:10.21037/jtd.2018.12.80 · Cited by 37
“Particularly chromosomal doubling caused by missegregation of chromosomes and cytokinesis failure has been shown to accelerate cancer evolution (78).”
BackgroundMitotic motor CENP-E cooperates with PRC1 in temporal control of central spindle assembly
Liu, X., Xu, L., Li, J., Yao, P. Y., Wang, W., Ismail, H., Wang, H., Liao, B., Yang, Z., Ward, T. L., et al. (2019) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjz051 · Cited by 34
cGAS-STING pathway expression as a prognostic tool in NSCLC
Gammelgaard, K. R., Sandfeld‐Paulsen, B., Godsk, S. H., Demuth, C., Meldgaard, P., Sørensen, B. S., & Jakobsen, M. R. (2021) · Translational Lung Cancer Research · doi:10.21037/tlcr-20-524 · Cited by 35
The cGAS-STING Pathway in Hematopoiesis and Its Physiopathological Significance
Liao, W., Du, C., & Wang, J. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.573915 · Cited by 34
Evolution and lineage dynamics of a transmissible cancer in Tasmanian devils
Kwon, Y. M., Gori, K. C., Park, N., Potts, N., Swift, K., Wang, J., Stammnitz, M. R., Cannell, N., Baez‐Ortega, A., Comte, S., et al. (2020) · PLoS Biology · doi:10.1371/journal.pbio.3000926 · Cited by 38
Advances in Lung Cancer Driver Genes Associated With Brain Metastasis
Kang, Y., Jin, Y. T., Li, Q., & Yuan, X. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2020.606300 · Cited by 37
“found that metastatic tumors contain a large number of differentially upregulated EMT- and inflammation-related genes (90).”
BackgroundMolnar, B. A., Galamb, O., Kalmár, A., Barták, B. K., Nagy, Z. B., Tóth, K., Tulassay, Z., Igaz, P., & Dank, M. (2019) · Expert Review of Molecular Diagnostics · doi:10.1080/14737159.2019.1613891 · Cited by 35
Double-checking chromosome segregation
Maiato, H., & Silva, S. D. R. (2023) · The Journal of Cell Biology · doi:10.1083/jcb.202301106 · Cited by 37
“Somatic cell aneuploidy is implicated in tumorigenesis, genomic instability, tumor evolution, metastasis, drug resistance, and reduced cancer patient survival, whereas germline aneuploidy directly accounts for infertility, pregnancy loss, and developmental disorders (Bakhoum et al., 2018; Crasta et al., 2012; Hassold…”
BackgroundHigh-grade serous ovarian carcinoma organoids as models of chromosomal instability
Vias, M., Gavarró, L. M., Sauer, C. M., Sanders, D. A., Piskorz, A., Couturier, D., Ballereau, S. J., Hernando, B., Schneider, M. P., Hall, J. A. M., et al. (2023) · eLife · doi:10.7554/elife.83867 · Cited by 35
The dark side of ferroptosis in pancreatic cancer
Liu, J., Dai, E., Kang, R., Kroemer, G., & Tang, D. (2021) · OncoImmunology · doi:10.1080/2162402x.2020.1868691 · Cited by 35
Association of homozygous variants of STING1 with outcome in human cervical cancer
Lubbers, J. M., Koopman, B., de Klerk‐Sluis, J. M., van Rooij, N., Plat, A., Pijper, H., Koopman, T., van Hemel, B. M., Hollema, H., Wisman, B. A., et al. (2020) · Cancer Science · doi:10.1111/cas.14680 · Cited by 35
Das, C., Adhikari, S., Bhattacharya, A., Chakraborty, S., Mondal, P., Yadav, S. S., Adhikary, S., Hunt, C. R., Yadav, K. K., Pandita, S., et al. (2023) · Cancer Research · doi:10.1158/0008-5472.can-22-3015 · Cited by 39
Nucleotide metabolism in the regulation of tumor microenvironment and immune cell function
Madsen, H. B., Peeters, M. J. W., Straten, P. T., & Desler, C. (2023) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2023.103008 · Cited by 35
“However, tumor development and the TME are highly complex and their link to cytoplasmic DNA signaling seems to be dependent on tumor stage and type [25].”
BackgroundCancer cells restrict immunogenicity of retrotransposon expression via distinct mechanisms
Sun, S., You, E., Hong, J., Hoyos, D., Priore, I. S. D., Tsanov, K. M., Mattagajasingh, O., Gioacchino, A. D., Marhon, S. A., Chacon-Barahona, J. A., et al. (2024) · Immunity · doi:10.1016/j.immuni.2024.10.015 · Cited by 35
From Colitis to Cancer: An Evolutionary Trajectory That Merges Maths and Biology
Bakir, I. A., Curtius, K., & Graham, T. A. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02368 · Cited by 33
“In aneuploid cancers, activation of the cGAS-STING pathway does not generate the expected downstream canonical NFκB and type I interferon signaling, but rather drives the non-canonical NFκB signaling cascade more typically seen in myeloid-derived cells, which the authors speculate may represent a form of immune mimicr…”
BackgroundMcGrail, D. J., Pilie, P. G., Dai, H., Lam, T., Liang, Y., Voorwerk, L., Kok, M., Zhang, X. H.-F., Rosen, J. M., Heimberger, A. B., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abe6201 · Cited by 36
Ciani, Y., Fedrizzi, T., Prandi, D., Lorenzin, F., Locallo, A., Gasperini, P., Franceschini, G. M., Benelli, M., Elemento, O., Fava, L. L., et al. (2021) · Cell Systems · doi:10.1016/j.cels.2021.10.001 · Cited by 35
“Following (Bakhoum et al., 2018), we adapted wGII to whole exome sequencing data by:”
MethodSelf-citationInterferon Signaling in Estrogen Receptor–positive Breast Cancer: A Revitalized Topic
Fu, X., Angelis, C. D., & Schiff, R. (2021) · Endocrinology · doi:10.1210/endocr/bqab235 · Cited by 33
Satellite DNAs in Health and Disease
Ugarković, Đ., Sermek, A., Ljubić, S., & Feliciello, I. (2022) · Genes · doi:10.3390/genes13071154 · Cited by 34
Huang, M., Cha, Z., Liu, R., Lin, M., Gafoor, N. A., Kong, T., Ge, F., & Chen, W. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1399926 · Cited by 36
Targeting the loss of cGAS / STING signaling in cancer
Sasaki, N., Homme, M., & Kitajima, S. (2023) · Cancer Science · doi:10.1111/cas.15913 · Cited by 34
Zhang, P., Hu, X., Li, Z., Liu, Q., Liu, L., Jin, Y.-Y., Liu, S., Zhao, X., Wang, J., Hao, D., et al. (2024) · Science Immunology · doi:10.1126/sciimmunol.adj5465 · Cited by 36
Breaking barriers: The cGAS‐STING pathway as a novel frontier in cancer immunotherapy
Yan, Y., Tan, X., Song, B., Yi, M., Chu, Q., & Wu, K. (2025) · 癌症：英文版 · doi:10.1002/cac2.70067 · Cited by 35
Qi, J., He, J., Liu, C.-B., Jin, S., Gao, R., Yang, X., Bai, H., & Ma, Y. (2020) · MedComm · doi:10.1002/mco2.22 · Cited by 35
Croce, S., & Chibon, F. (2020) · Genes Chromosomes and Cancer · doi:10.1002/gcc.22906 · Cited by 33
“state in which the cell gains or loses genetic material, promotes the development of chromosomal structural alterations.(31,32) When chromosomal rearrangements are unbalanced, they lead to loss or gain of genetic material.”
BackgroundPu, F., Chen, F., Liu, J., Zhang, Z., & Shao, Z. (2021) · OncoTargets and Therapy · doi:10.2147/ott.s298958 · Cited by 34
Interplay of cGAS with chromatin
Wischnewski, M., & Ablasser, A. (2021) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2021.05.011 · Cited by 35
Lynch, A. R., Arp, N. L., Zhou, A. S., Weaver, B. A. A., & Burkard, M. E. (2022) · eLife · doi:10.7554/elife.69799 · Cited by 31
Jungles, K. M., Holcomb, E. A., Pearson, A. N., Jungles, K. R., Bishop, C. R., Pierce, L. J., Green, M. D., & Speers, C. W. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.1022542 · Cited by 36
“Chromosomal instability (CIN)—another hallmark of cancer—occurs following chromosomal segregation errors during mitosis and can also activate the cGAS/STING pathway in cancer cells (70, 78).”
BackgroundInfluentialMitochondrial Contribution to Inflammation in Diabetic Kidney Disease
Mitrofanova, A. V., Fontanella, A. M., Burke, G. W., Merscher, S., & Fornoni, A. (2022) · Cells · doi:10.3390/cells11223635 · Cited by 35
Alhaddad, L., Chuprov‐Netochin, R. N., Pustovalova, M. V., Osipov, A. N., & Leonov, S. V. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24021228 · Cited by 34
“A wide range of tumorigenic phenotypes are caused by aneuploidy [59–61], many of which have been associated with mutant p53 GOF activities, including, but not limited to: altered proliferation [62], altered metabolism [63], transcriptional reprogramming and chemoresistance [64], migration [65], and invasion and metast…”
Lepage, C. C., Thompson, L. L., Larson, B., & McManus, K. J. (2020) · Cells · doi:10.3390/cells9020344 · Cited by 33
“In any case, the ultimate fate of a micronucleus is not clear; some may persist within daughter cells, while others may undergo micronuclear rupture [21,22], or re-join the primary nucleus during subsequent mitotic events, leading to a reduction in the number of micronuclei [17].”
BackgroundPerelli, L., Carbone, F., Zhang, L., Huang, J. K.-L., Le, C. N., Khan, H., Citron, F., Poggetto, E. D., Gutschner, T., Tomihara, H., et al. (2023) · Nature Cancer · doi:10.1038/s43018-023-00584-1 · Cited by 33
Self-citationA Markov chain for numerical chromosomal instability in clonally expanding populations
Elizalde, S., Laughney, A. M., & Bakhoum, S. F. W. (2018) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1006447 · Cited by 28
Self-citationDNA Repair Deficiency in Breast Cancer: Opportunities for Immunotherapy
Gilmore, E. S., McCabe, N., Kennedy, R. D., & Parkes, E. E. (2019) · Journal of Oncology · doi:10.1155/2019/4325105 · Cited by 32
“Moreover, chronic activation of cGAS-STING in chromosomally unstable tumors has been shown to result in STINGdependent metastasis [129].”
BackgroundInhibition of Haspin Kinase Promotes Cell-Intrinsic and Extrinsic Antitumor Activity
Melms, J. C., Vallabhaneni, S., Mills, C. E., Yapp, C., Chen, J.-Y., Morelli, E., Waszyk, P., Kumar, S., Deming, D., Moret, N., et al. (2019) · Cancer Research · doi:10.1158/0008-5472.can-19-2330 · Cited by 33
“Chromosomal instability (CIN) resulting from errors in mitotic segregation has been associated with increased metastatic potential through tonic STING activation (32), resulting in an immunosuppressive tumor environment (33).”
BackgroundReplication catastrophe induced by cyclic hypoxia leads to increased APOBEC3B activity
Bader, S. B., Ma, T. S., Simpson, C. J., Liang, J., Maezono, S. E. B., Olcina, M. M., Buffa, F. M., & Hammond, E. M. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab551 · Cited by 32
“This finding raised the possibility that cyclic hypoxia-induced cGAS could lead to NF- B activity and consequent A3B expression (44).”
BackgroundThe Cytosolic DNA-Sensing cGAS-STING Pathway in Liver Diseases
Wang, Z., Chen, N., Li, Z., Xu, G., Zhan, X., Tang, J., Xiao, X., & Bai, Z. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.717610 · Cited by 32
“non-canonical nuclear factor kB (NF-kB), mitogen-activated protein (MAP) kinases, and signal transducer and activator of transcription (STAT) transcription factors (McWhirter et al., 2009; Bakhoum et al., 2018).”
BackgroundHaimovici, A., Höfer, C., Badr, M. T., Haghighi, E. B., Amer, T., Boerries, M., Bronsert, P., Glavynskyi, I., Fanfone, D., Ichim, G., et al. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-04768-y · Cited by 34
“CAD is a determinant of metastatic potential in vivo Spontaneous activity of caspases and CAD has been reported to drive growth rates of subcutaneously xenotransplanted tumors in mice [9], while STING has been found to regulate metastasis [13].”
BackgroundInfluentialCells in the polyaneuploid cancer cell (PACC) state have increased metastatic potential
Mallin, M. M., Kim, N., Choudhury, M. I., Lee, S. J., An, S. S., Sun, S. X., Κωνσταντόπουλος, Κ., Pienta, K. J., & Amend, S. R. (2023) · Clinical & Experimental Metastasis · doi:10.1007/s10585-023-10216-8 · Cited by 31
“Furthermore, work on chromosomal-instability-induced senescence demonstrates that senescent tetraploid cells contributed to increased tumorigenic and metastatic potential [80, 81].”
BackgroundTargeting the DNA replication stress phenotype of KRAS mutant cancer cells
Zubaidi, T. A., Gehrisch, O. H. F., Genois, M., Liu, Q., Lü, S., Kung, J., Xie, Y., Schuemann, J., Lu, H., Hata, A. N., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-83142-y · Cited by 34
Interferon restores replication fork stability and cell viability in BRCA-defective cells via ISG15
Moro, R. N., Biswas, U., Kharat, S. S., Duzanic, F. D., Das, P., Stavrou, M., Raso, M. C., Freire, R., Chaudhuri, A. R., Sharan, S. K., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-41801-w · Cited by 35
“…context, as acute in fl ammation has immune-stimulatory effects against malignancies while chronic in fl ammation may promote cancer development 7,9 – 11 , and can even be exploited for immunotherapeutic purposes 12 , underlining the importance of better understanding the links between replication…”
Wu, S., Wang, B., Li, H., Wang, H., Du, S., Huang, X., Fan, Y., Gao, Y., Gu, L., Huang, Q., et al. (2024) · Oncogene · doi:10.1038/s41388-024-03013-4 · Cited by 32
RetractedSimovic-Lorenz, M., & Ernst, A. (2024) · Nature reviews. Cancer · doi:10.1038/s41568-024-00769-5 · Cited by 33
“However, activation of the cGAS–STING pathway could be a double-edged sword in cancer owing to emerging data suggesting that activation of the cGAS–STING pathway in tumours with high levels of chromosomal instability can promote the invasion, metastasis and survival of cancer cells 124,125 .”
Targeting STING to generate therapeutic anti-tumor immunity
Fahey, C. G., Cordova, A. F., Gedeon, P. C., & Barbie, D. A. (2025) · Cancer Cell · doi:10.1016/j.ccell.2025.12.002 · Cited by 36
Ye, Y., Jiao, H., Wang, S., Xiao, Z., Zhang, D., Qiu, J., Zhang, L., Zhao, Y., Li, T., Li-Liang, et al. (2018) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-018-0958-1 · Cited by 31
Streptavidin Promotes DNA Binding and Activation of cGAS to Enhance Innate Immunity
Zhang, Y., Ma, Z., Wang, Y., Boyer, J. A., Ni, G., Cheng, L., Su, S., Zhang, Z., Zhu, Z., Qian, J., et al. (2020) · iScience · doi:10.1016/j.isci.2020.101463 · Cited by 32
Delespaul, L., Gélabert, C., Lesluyes, T., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-78502-z · Cited by 31
Reece, A. S., & Hulse, G. K. (2021) · BMC Cancer · doi:10.1186/s12885-021-07924-3 · Cited by 31
HER2 Activation and Endocrine Treatment Resistance in HER2-negative Breast Cancer
Mazumder, A., Shiao, S. L., & Haricharan, S. (2021) · Endocrinology · doi:10.1210/endocr/bqab153 · Cited by 32
Mitotic protein kinase-driven crosstalk of machineries for mitosis and metastasis
Kim, C.-H., Kim, D., Kim, D., Min, G.-H., Park, J., Kim, Y.-B., Sung, C. K., & Yim, H. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-022-00750-y · Cited by 34
Klaasen, S. J., & Kops, G. J. P. L. (2022) · Cells · doi:10.3390/cells11223564 · Cited by 36
Wang, Y., Liu, Y., Zhang, J., Peng, Q., Wang, X., Xiao, X., & Shi, K. (2024) · Acta Biomaterialia · doi:10.1016/j.actbio.2024.01.008 · Cited by 31
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
