ArticleCancer discovery2017
APC/C Dysfunction Limits Excessive Cancer Chromosomal Instability.
Article in Cancer discovery, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 116 citations in OpenAlex.
- MPS1 inhibition as an anticancer strategy: where do we stand?Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2026Review
- Chromosomal instability in cancer: sources, consequences and new therapeutic opportunities.Signal transduction and targeted therapy · 2026Review
- Impact of Chromosomal Instability and Aneuploidy in Cancer Development.Annual review of cancer biology · 2026Article
- Multi-Omics Identification of UBE2C as a Prognostic Biomarker and Therapeutic Target Linked to Topotecan Sensitivity in Cervical Cancer.Oncology research · 2026Article
- The scaffold protein PRR14L links the PP2A-TACC3 axis to mitotic fidelity and sensitivity to MPS1 inhibition.bioRxiv : the preprint server for biology · 2025Article
- A signature of correlated CDC20 and UBCH10 expression indicates poor prognosis in primary head and neck squamous cell carcinoma.BMC cancer · 2025Article
- Anapc5 and Anapc7 as genetic modifiers of KIF18A function in fertility and mitotic progression.Scientific reports · 2025Article
- Loss of G1-phase CDK-inhibition biases instability between genomic regions by unevenly reducing activity among replication origins.iScience · 2025Article
- AI-Guided Chemotherapy Optimization in Lung Cancer Using Genomic and Survival Data.Journal of personalized medicine · 2025Article
- Infertile females with biallelic mutations in APC/C genes are characterized by oocyte or early embryo defects.Journal of assisted reproduction and genetics · 2025Article
- lncreased risk of slippage upon disengagement of the mitotic checkpoint.PLoS computational biology · 2025Article
- Tumour hypoxia in driving genomic instability and tumour evolution.Nature reviews. Cancer · 2025Review
- Mosaic variegated aneuploidy in development, ageing and cancer.Nature reviews. Genetics · 2024Review
- Molecular Alterations Associated with Histologically Overt Stromal Response in Patients with Prostate Cancer.International journal of molecular sciences · 2024Article
- Article
- Cytidine Deaminase Resolves Replicative Stress and Protects Pancreatic Cancer from DNA-Targeting Drugs.Cancer research · 2024Article
- The two sides of chromosomal instability: drivers and brakes in cancer.Signal transduction and targeted therapy · 2024Review
- TRMT13 inhibits the growth of papillary thyroid cancer by targeting ANAPC4.Acta biochimica et biophysica Sinica · 2024Article
- Weakened APC/C activity at mitotic exit drives cancer vulnerability to KIF18A inhibition.The EMBO journal · 2024Article
- Chromosomal instability in aneuploid acute lymphoblastic leukemia associates with disease progression.EMBO molecular medicine · 2024Article
14 more citing papers are in PubMed but not listed here.
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18 authors at 2 institutions in 2 countries.
Funding
Abstract
Intercellular heterogeneity, exacerbated by chromosomal instability (CIN), fosters tumor heterogeneity and drug resistance. However, extreme CIN correlates with improved cancer outcome, suggesting that karyotypic diversity required to adapt to selection pressures might be balanced in tumors against the risk of excessive instability. Here, we used a functional genomics screen, genome editing, and pharmacologic approaches to identify CIN-survival factors in diploid cells. We find partial anaphase-promoting complex/cyclosome (APC/C) dysfunction lengthens mitosis, suppresses pharmacologically induced chromosome segregation errors, and reduces naturally occurring lagging chromosomes in cancer cell lines or following tetraploidization. APC/C impairment caused adaptation to MPS1 inhibitors, revealing a likely resistance mechanism to therapies targeting the spindle assembly checkpoint. Finally, CRISPR-mediated introduction of cancer somatic mutations in the APC/C subunit cancer driver gene CDC27 reduces chromosome segregation errors, whereas reversal of an APC/C subunit nonsense mutation increases CIN. Subtle variations in mitotic duration, determined by APC/C activity, influence the extent of CIN, allowing cancer cells to dynamically optimize fitness during tumor evolution. SIGNIFICANCE: We report a mechanism whereby cancers balance the evolutionary advantages associated with CIN against the fitness costs caused by excessive genome instability, providing insight into the consequence of CDC27 APC/C subunit driver mutations in cancer. Lengthening of mitosis through APC/C modulation may be a common mechanism of resistance to cancer therapeutics that increase chromosome segregation errors. Cancer Discov; 7(2); 218-33. ©2017 AACR.See related commentary by Burkard and Weaver, p. 134This article is highlighted in the In This Issue feature, p. 115.
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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.