The role of aneuploidy in promoting and suppressing tumors

Impaired mitotic checkpoint signaling can both promote and suppress tumors. The mitotic checkpoint targets Cdc20, the specificity factor of the ubiquitin ligase that promotes anaphase by targeting cyclin B and securin for destruction. In this issue, Li et al. (2009. J. Cell Biol. doi:10.1083/jcb.200904020) use gene replacement to produce mice expressing a Cdc20 mutant that cannot be inhibited by the mitotic checkpoint. In addition to the expected aneuploidy, these animals have a high tumor incidence that is likely caused by persistent aneuploidy coupled with nonmitotic functions of mutant Cdc20.

• Publication year

  2009

• Venue

  Journal of Cell Biology

• Publication date

  2009-06-15

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1083/jcb.200905098PMID 19528293PMCID 2711620
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Loss of spindle assembly checkpoint–mediated inhibition of Cdc20 promotes tumorigenesis in mice

  2009influential reference
• Examining the link between chromosomal instability and aneuploidy in human cells

  2008cited by this paper
• MAD2 interacts with DNA repair proteins and negatively regulates DNA damage repair.

  2008cited by this paper
• Aneuploidy Affects Proliferation and Spontaneous Immortalization in Mammalian Cells

  2008cited by this paper
• Bub1 mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis

  2007influential reference
• Mad2 overexpression promotes aneuploidy and tumorigenesis in mice.

  2007influential reference
• Aneuploidy acts both oncogenically and as a tumor suppressor.

  2007cited by this paper
• Bub1 maintains centromeric cohesion by activation of the spindle checkpoint.

  2007cited by this paper
• Heterozygous deletion of mitotic arrest-deficient protein 1 (MAD1) increases the incidence of tumors in mice.

  2007influential reference
• Aneuploidy and cancer: from correlation to causation.

  2006cited by this paper
• Does aneuploidy cause cancer?

  2006cited by this paper
• Early aging–associated phenotypes in Bub3/Rae1 haploinsufficient mice

  2006influential reference
• Caspases-dependent cleavage of mitotic checkpoint proteins in response to microtubule inhibitor.

  2005cited by this paper
• Human spindle checkpoint kinase Bub1 is cleaved during apoptosis

  2005cited by this paper
• Colonic tumorigenesis in BubR1+/-ApcMin/+ compound mutant mice is linked to premature separation of sister chromatids and enhanced genomic instability.

  2005cited by this paper
• Complete loss of the tumor suppressor MAD2 causes premature cyclin B degradation and mitotic failure in human somatic cells.

  2004cited by this paper
• Mitotic checkpoint function in the formation of gross chromosomal rearrangements in Saccharomyces cerevisiae.

  2004cited by this paper
• WD repeat‐containing mitotic checkpoint proteins act as transcriptional repressors during interphase

  2004cited by this paper
• BubR1 insufficiency causes early onset of aging-associated phenotypes and infertility in mice

  2004influential reference
• Lethality to human cancer cells through massive chromosome loss by inhibition of the mitotic checkpoint.

  2004cited by this paper
• S-phase checkpoint controls mitosis via an APC-independent Cdc20p function

  2003cited by this paper
• Rae1 is an essential mitotic checkpoint regulator that cooperates with Bub3 to prevent chromosome missegregation

  2003cited by this paper
• MAD2 haplo-insufficiency causes premature anaphase and chromosome instability in mammalian cells

  2001influential reference
• Chromosome missegregation and apoptosis in mice lacking the mitotic checkpoint protein Mad2.

  2000cited by this paper
• Cdc20, a β-transducin homologue, links RAD9-mediated G2/M checkpoint control to mitosis in Saccharomyces cerevisiae

  1996cited by this paper

• Genomic Instability and Shear Stress Influence Quantum Dot- Induced Endothelial Cell Responses and Gene Expression

  2025cites this paper
• Polyploid giant cancer cells: A novel target in future cancer therapy.

  2025cites this paper
• Triage of women with positive HPV: comparing DNA ploidy analysis with HPV 16/18 genotyping and cervical cytology

  2025cites this paper
• A signature of correlated CDC20 and UBCH10 expression indicates poor prognosis in primary head and neck squamous cell carcinoma

  2025cites this paper
• High CDC20 levels increase sensitivity of cancer cells to MPS1 inhibitors

  2025cites this paper
• PP2A Promotes the Symmetric Division of MUC1‐Dominant Cancer Stem‐Like Cells in Small Cell Lung Cancer

  2025cites this paper
• Emerging role and function of SPDL1 in human health and diseases

  2024cites this paper
• The potential of aryl hydrocarbon receptor as receptors for metabolic changes in tumors

  2024cites this paper
• Contribution of histone variants to aneuploidy: a cancer perspective

  2023cites this paper
• CDC20-Mediated hnRNPU Ubiquitination Regulates Chromatin Condensation and Anti-Cancer Drug Response

  2022cites this paper
• The classification of life

  2022cites this paper
• Nek2 Kinase Signaling in Malaria, Bone, Immune and Kidney Disorders to Metastatic Cancers and Drug Resistance: Progress on Nek2 Inhibitor Development

  2022cites this paper
• Discovery of the First Examples of Threonine Tyrosine Kinase PROTAC Degraders.

  2022cites this paper
• Functional analysis of recurrent non-coding variants in human melanoma

  2022cites this paper
• A Traceable Cancer Model: DNA Damage, Fragile Site-SMGs, Mitotic Slippage, 4n-Genome-Reduction to Fitness-Gained, Initiating, 2n First Cells

  2021cites this paper
• Quantifying chromosomal instability from intratumoral karyotype diversity using agent-based modeling and Bayesian inference

  2021cites this paper
• Polyploidy formation in cancer cells: how a Trojan horse is born.

  2021cites this paper
• Aneuploid IMR90 cells induced by depletion of pRB, DNMT1 and MAD2 show a common gene expression signature.

  2020cites this paper
• “Amyloid‐beta accumulation cycle” as a prevention and/or therapy target for Alzheimer's disease

  2020cites this paper
• What we learn when our data are abnormal

  2020cites this paper
• Reduced expression of CENP-E contributes to the development of hepatocellular carcinoma and is associated with adverse clinical features.

  2019influential citation
• Live Cell Interferometry: A Novel Quantitative Phase Imaging Technique for Rapid Characterizations of Tumor Heterogeneity, Drug Resistance, Cell Fates and Biophysical Properties

  2019cites this paper
• Genomic Instability in Cancer II: 4N-Skewed (90°) Reductive Division via Fragile Sites to Fitness Increase for Solid and Hematological Cancer Beginnings

  2019cites this paper
• Elevated signature of a gene module coexpressed with CDC20 marks genomic instability in glioma

  2019cites this paper
• Mechanisms of kinesin‐7 CENP‐E in kinetochore–microtubule capture and chromosome alignment during cell division

  2019cites this paper
• Identifying fates of cancer cells exposed to mitotic inhibitors by quantitative phase imaging.

  2019cites this paper
• Critical role of mitosis in spontaneous late-onset Alzheimer’s disease; from a Shugoshin 1 cohesinopathy mouse model

  2018cites this paper
• Genomic Instability in Cancer I: DNA-Repair Triggering Primitive Hereditary 4n-Skewed, Amitotic Division-System, the Culprit in EMT/MET/Metaplasia Cancer-Concepts

  2018cites this paper
• Redefining Disease Causality

  2018cites this paper
• Smurf1 controls S phase progression and tumorigenesis through Wee1 degradation

  2017cites this paper
• Manipulation of DNA Repair Proficiency in Mouse Models of Colorectal Cancer

  2016cites this paper
• Downregulation of CDC27 inhibits the proliferation of colorectal cancer cells via the accumulation of p21Cip1/Waf1

  2016cites this paper
• Multipolar mitosis and aneuploidy after chrysotile treatment: a consequence of abscission failure and cytokinesis regression

  2016cites this paper
• Nucleus, Nuclear Structure, and Nuclear Functions: Pathogenesis of Nuclear Abnormalities in Cancer

  2016cites this paper
• p14ARF Prevents Proliferation of Aneuploid Cells by Inducing p53‐Dependent Apoptosis

  2016cites this paper
• SECURIN, CDC20 AND CDC27 IN PREDICTING THE OUTCOME OF BREAST CANCER

  2015cites this paper
• Aneuploidy causes premature differentiation of neural and intestinal stem cells

  2015cites this paper
• Genomic DNA Copy Number Aberrations, Histological Diagnosis, Oral Subsite and Aneuploidy in OPMDs/OSCCs

  2015influential citation
• Centrosome amplification, chromosomal instability and cancer: mechanistic, clinical and therapeutic issues

  2015cites this paper
• A Motif from Lys216 to Lys222 in Human BUB3 Protein Is a Nuclear Localization Signal and Critical for BUB3 Function in Mitotic Checkpoint*

  2015cites this paper
• Usp7 protects genomic stability by regulating Bub3

  2014cites this paper
• Clinical application of DNA ploidy to cervical cancer screening: A review.

  2014cites this paper
• Diferentes abordagens para o entendimento da aneuploidia: interferindo na mitose com o uso de crisotila e vincristina

  2014cites this paper
• Chromosomal alterations in exfoliated urothelial cells from bladder cancer cases and healthy men: a prospective screening study

  2014cites this paper
• Formaldehyde induces micronuclei in mouse erythropoietic cells and suppresses the expansion of human erythroid progenitor cells.

  2014cites this paper
• The mechanism of chromosome loss induced by an aneugen in human lymphoid cells

  2014cites this paper
• Chromosome loss caused by DNA fragmentation induced in main nuclei and micronuclei of human lymphoblastoid cells treated with colcemid.

  2014cites this paper
• Human Interphase Chromosomes

  2013cites this paper
• Tubulin cofactor A functions as a novel positive regulator of ccRCC progression, invasion and metastasis

  2013cites this paper
• Multi-Layered Cancer Chromosomal Instability Phenotype

  2013cites this paper
• Low cdc27 and high securin expression predict short survival for breast cancer patients

  2013cites this paper
• Advanced quantitative mass spectrometry applied to aneuploidy and apoptosis.

  2013cites this paper
• Interphase Chromosomes of the Human Brain: The Biological and Clinical Meaning of Neural Aneuploidy

  2013cites this paper
• Integrins in Tumorigenesis and Cancer Cell Invasion

  2013cites this paper
• A Screen for Selective Killing of Cells with Chromosomal Instability Induced by a Spindle Checkpoint Defect

  2012influential citation
• Never tear us apart – the importance of centrosome clustering

  2012cites this paper
• Transforming Fusions of FGFR and TACC Genes in Human Glioblastoma

  2012cites this paper
• Securin predicts aneuploidy and survival in breast cancer

  2012cites this paper
• The stable traits of melanoma genetics: an alternate approach to target discovery

  2012cites this paper
• Genome instability: Does genetic diversity amplification drive tumorigenesis?

  2012cites this paper
• Genome reversion process of endopolyploidy confers chromosome instability on the descendent diploid cells

  2012cites this paper
• Weighted Frequent Gene Co-expression Network Mining to Identify Genes Involved in Genome Stability

  2012cites this paper
• Mitotic spindle (DIS)orientation and DISease: Cause or consequence?

  2012cites this paper
• Causes and consequences of aneuploidy in cancer

  2012cites this paper
• Evolutionary karyotypic theory of cancer versus conventional cancer gene mutation theory

  2012cites this paper
• Nuclear remodeling as a mechanism for genomic instability in cancer.

  2011cites this paper
• Cdk1-phosphorylated CUEDC2 promotes spindle checkpoint inactivation and chromosomal instability

  2011cites this paper
• Genetic disruption of aurora B uncovers an essential role for aurora C during early mammalian development

  2011cites this paper
• Genetic disruption of aurora B uncovers an essential role for aurora C during early mammalian development

  2011cites this paper
• The Effects of Polo-like Kinase 4 on Chromosomal Stability, Cell Migration and Tumourigenesis

  2011influential citation
• Targeting aneuploid cancer cells

  2011cites this paper
• Centromere fission, not telomere erosion, triggers chromosomal instability in human carcinomas

  2011cites this paper
• Overexpression of Ubiquitin Specific Protease 44 (USP44) Induces Chromosomal Instability and Is Frequently Observed in Human T-Cell Leukemia

  2011cites this paper
• Cytokinesis and cancer

  2010cites this paper
• Plk4 is required for cytokinesis and maintenance of chromosomal stability

  2010cites this paper
• Pleiotropic functions of Rho GTPase signaling: a Trojan horse or Achilles' heel for breast cancer treatment?

  2010cites this paper
• Pediatric brain tumor cancer stem cells: cell cycle dynamics, DNA repair, and etoposide extrusion

  2010cites this paper
• The Prp19 complex and the Usp4Sart3 deubiquitinating enzyme control reversible ubiquitination at the spliceosome.

  2010cites this paper
• Targeting the mitotic checkpoint for cancer therapy with NMS-P715, an inhibitor of MPS1 kinase.

  2010cites this paper
• Targeting karyotypic complexity and chromosomal instability of cancer cells.

  2010cites this paper
• Chromosome missegregation causes colon cancer by APC loss of heterozygosity.

  2010cites this paper
• Mps1 directs the assembly of Cdc20 inhibitory complexes during interphase and mitosis to control M phase timing and spindle checkpoint signaling

  2010cites this paper
• The spindle-assembly checkpoint, aneuploidy, and gastrointestinal cancer.

  2010cites this paper
• Overexpression of the E2 ubiquitin–conjugating enzyme UbcH10 causes chromosome missegregation and tumor formation

  2010cites this paper
• Jcb: Article

  year unknowncites this paper
• Molecular and Cellular Pathobiology the Aryl Hydrocarbon Receptor Functions as a Tumor Suppressor of Liver Carcinogenesis

  year unknowncites this paper