ArticleNature2018
Chromosomal instability drives metastasis through a cytosolic DNA response.
4 registry-linked trialsAbstract read
In one paragraph
Article in Nature, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 1,013 papers.
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1,013citing papers in PubMed
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Ultrasensitive Chromosomal Aneuploidy Detection (UCAD) in Urine Exfoliated Cells for Diagnosis of Urothelial Carcinoma in in Urine Exfoliated Cells
Application of Ultrasensitive Chromosomal Aneuploidy Detection (UCAD) as a Surrogate Biomarker of Minimal Residual Diseases for Multiple Myeloma Patients
A Prospective, Multi-centre, Single-blinded Study of UroCAD for Urothelial Carcinoma Diagnosis and Follow-up
A Prospective, Multi-centre, Single-blinded Study of UCAD for Diagnosing Benign or Malignant Biliary Obstruction and Follow-up
Who cites it
1,013 citing papers in PubMed.
- Remodeling of innate antiviral immunity in aging.Cell insight · 2026Review
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- The cGAS-STING/MITA pathway in innate antiviral immunity and beyond.Cell insight · 2026Review
- Clinical metastatic cancer from initiation to colonization: emerging challenges and breakthroughs.Oncogene · 2026Review
- Organelle-Selective Autophagy in Cancer Immunotherapy: Mitophagy and Nucleophagy-Related Nuclear Quality Control as Regulators of Tumor-Immune Interactions.International journal of molecular sciences · 2026Review
- The dual immune landscape of homologous recombination-deficient tumors: mechanisms and therapeutic implications.Cancer metastasis reviews · 2026Review
- Replication stress in cancer: origins, consequences and therapeutic opportunities.Nature reviews. Cancer · 2026Review
- Young Aggressive Prostate Tumors Exhibit Increased Genomic Instability and an Exploratory RNA-CNA-Concordant Transcriptomic Pattern.International journal of molecular sciences · 2026Article
- Chromosomal instability in cancer: sources, consequences and new therapeutic opportunities.Signal transduction and targeted therapy · 2026Review
- Melanoma evolution in the lymph node shapes systemic outcomes.bioRxiv : the preprint server for biology · 2026Article
- Modeling meningioma in vitro in the omics era.Human cell · 2026Review
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- Genomic landscape and tumor immune microenvironment of osteosarcoma: Bridging mechanistic insights to precision therapeutics.Bone reports · 2026Review
- A versatile cGAMP reporter reveals principles of cGAS activation by DNA damage and chromosome instability.Nature cell biology · 2026Article
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- Chronic interferon signaling at baseline is associated with acquired resistance to immunotherapy in metastatic melanoma.Cell reports. Medicine · 2026Article
- EWSR1::FLI1 promotes neocentromere formation in ewing sarcoma cells.Cell reports · 2026Article
- cGAS-STING pathway activation drives the cold-to-hot tumor transition and sensitizes immunotherapy.Cancer biology & medicine · 2026Review
- Residual Lung Cancer After Incomplete Microwave Ablation Exhibits cGAS-STING-ZEB1-Driven Malignant Progression.Cancers · 2026Article
- The kinase CK1α coordinates the initiation and termination of the cGAS-STING pathway.Cell death and differentiation · 2026Article
953 more citing papers are in PubMed but not listed here.
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Authors and funding
33 authors.
Samuel F BakhoumDepartment of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
Bryan NgoSandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, New York 10065, USA.
Ashley M LaughneyCancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
Julie-Ann CavalloDepartment of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
Charles J MurphySandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, New York 10065, USA.
Peter LyLudwig Institute for Cancer Research, University of California San Diego, La Jolla, California 92093, USA.
Pragya ShahNancy E. and Peter C. Meinig School of Biomedical Engineering & Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, New York 14850, USA.
Roshan K SriramSandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, New York 10065, USA.
Thomas B K WatkinsThe Francis Crick Institute, London NW1 1AT, UK.
Neil K TaunkDepartment of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
Mercedes DuranDepartment of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
Chantal PauliInstitute for Pathology and Molecular Pathology, University Hospital Zurich, Zurich 8091, Switzerland.
Christine ShawMolecular Cytogenetics Core, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
Kalyani ChadalavadaMolecular Cytogenetics Core, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
Vinagolu K RajasekharDepartment of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
Giulio GenoveseThe Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.
Subramanian VenkatesanUCL Cancer Institute, London WC1E 6BT, UK.
Nicolai J BirkbakThe Francis Crick Institute, London NW1 1AT, UK.
Nicholas McGranahanThe Francis Crick Institute, London NW1 1AT, UK.
Mark LundquistSandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, New York 10065, USA.
Quincey LaPlantDepartment of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
John H HealeyDepartment of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
Olivier ElementoSandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, New York 10065, USA.
Christine H ChungMoffitt Cancer Center, Tampa, Florida 33612, USA.
Nancy Y LeeDepartment of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
Marcin ImielenskiSandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, New York 10065, USA.
Gouri NanjangudMolecular Cytogenetics Core, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
Dana Pe'erComputational Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
Don W ClevelandLudwig Institute for Cancer Research, University of California San Diego, La Jolla, California 92093, USA.
Simon N PowellDepartment of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
Jan LammerdingNancy E. and Peter C. Meinig School of Biomedical Engineering & Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, New York 14850, USA.
Charles SwantonThe Francis Crick Institute, London NW1 1AT, UK.
Lewis C CantleySandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, New York 10065, USA.
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Elisa de Stanchina · 1985 to 2026
$347.4MRole of Phosphoinositides and Protein Kinases in the control of Cancer MetabolismR35CA197588 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI LEWIS C. CANTLEY · 2016 to 2026
$10.2MProject 3: Physical and Metabolic Constraints of Cancer Cell InvasionU54CA210184 · NCI · CORNELL UNIVERSITY · PI SCHAFFER, CHRIS B · 2016 to 2020
$10.2MMechanisms of chromosome segregation, aneuploidy, and tumorigenesisR35GM122476 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Don W Cleveland · 2017 to 2026
$9.0MNuclear mechanics and mechanotransduction in muscular laminopathiesR01HL082792 · NHLBI · CORNELL UNIVERSITY · PI LAMMERDING, JAN · 2007 to 2023
$4.8MThe Response to a Site-Specific Blocked DNA Replication Fork in Human CancersR01CA187069 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI POWELL, SIMON N. · 2014 to 2018
$1.8MConnections and redundancy in the BRCA1-BRCA2 pathway of homologous recombinationR01CA169306 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI POWELL, SIMON N. · 2013 to 2017
$1.8MCell Division Errors as a Mechanism Driving Massive Genomic RearrangementsK99CA218871 · NCI · LUDWIG INSTITUTE FOR CANCER RES LTD · PI LY, PETER · 2017 to 2018
$236kCancer Research UK 17786Cancer Research UK 19310Cancer Research UK 20466Medical Research Council G0701935Medical Research Council MR/P014712/1NCI NIH HHS K99 CA218871NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA169306NCI NIH HHS R01 CA187069NCI NIH HHS R35 CA197588NCI NIH HHS U54 CA210184NHLBI NIH HHS R01 HL082792NIGMS NIH HHS R35 GM122476
Abstract
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.
Indexed as
Chromosomal InstabilityAnimalsBrain NeoplasmsBreast NeoplasmsCarcinoma, Squamous CellCell LineChromosome SegregationCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseCytosolDNA, NeoplasmFemaleHead and Neck NeoplasmsHumansInflammationMembrane ProteinsMesodermcGAS protein, humanCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseDNA, NeoplasmMembrane ProteinsNF-kappa BNucleotidyltransferasesSTING1 protein, humanSTING Protein
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Registered trials
NCT03998371ClinicalTrials.gov
NCT04122092ClinicalTrials.gov
NCT04432909ClinicalTrials.gov
NCT05237193ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.