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Dev Cell. 2017 Feb 6;40(3):313-322.e5. doi: 10.1016/j.devcel.2016.12.022. Epub 2017 Jan 26.

Centrosome Amplification Is Sufficient to Promote Spontaneous Tumorigenesis in Mammals.

Author information

1
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
2
European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen 9713 AV, the Netherlands.
3
Laboratory of Translational Genetics, Vesalius Research Center, VIB, 3000 Leuven, Belgium; Laboratory of Translational Genetics, Department of Oncology, KU Leuven, 3000 Leuven, Belgium.
4
CNRS UMR-5237, Centre de Recherche en Biochimie Macromoleculaire, University of Montpellier, Montpellier 34093, France.
5
San Diego Branch, Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA; Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
6
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: aholland@jhmi.edu.

Abstract

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.

KEYWORDS:

Plk4; aneuploidy; centriole; centrosome amplification; genomic instability; mitosis; tumorigenesis

PMID:
28132847
PMCID:
PMC5296221
DOI:
10.1016/j.devcel.2016.12.022
[Indexed for MEDLINE]
Free PMC Article

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