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Centrosome Amplification Is Sufficient to Promote Spontaneous Tumorigenesis in Mammals.

Developmental cell | 2017

Centrosome amplification is a common feature of human tumors, but whether this is a cause or a consequence of cancer remains unclear. Here, we test the consequence of centrosome amplification by creating mice in which centrosome number can be chronically increased in the absence of additional genetic defects. We show that increasing centrosome number elevated tumor initiation in a mouse model of intestinal neoplasia. Most importantly, we demonstrate that supernumerary centrosomes are sufficient to drive aneuploidy and the development of spontaneous tumors in multiple tissues. Tumors arising from centrosome amplification exhibit frequent mitotic errors and possess complex karyotypes, recapitulating a common feature of human cancer. Together, our data support a direct causal relationship among centrosome amplification, genomic instability, and tumor development.

Pubmed ID: 28132847 RIS Download

Associated grants

  • Agency: European Research Council, International
    Id: 294740
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM029513
  • Agency: NIGMS NIH HHS, United States
    Id: F31 GM122288
  • Agency: NIGMS NIH HHS, United States
    Id: R35 GM122476
  • Agency: European Research Council, International
    Id: 294740
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM114119
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK090868
  • Agency: NIGMS NIH HHS, United States
    Id: R37 GM029513

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