Centrosome loss results in an unstable genome and malignant prostate tumors
AffiliationUniv Arizona, Canc Ctr, Dept Cellular & Mol Med
Univ Arizona, Canc Ctr, Dept Pathol
MetadataShow full item record
PublisherNATURE PUBLISHING GROUP
CitationWang, M., Nagle, R.B., Knudsen, B.S. et al. Centrosome loss results in an unstable genome and malignant prostate tumors. Oncogene 39, 399–413 (2020). https://doi.org/10.1038/s41388-019-0995-z
RightsCopyright © The Author(s), under exclusive licence to Springer Nature Limited 2019
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AbstractLocalized, nonindolent prostate cancer (PCa) is characterized by large-scale genomic rearrangements, aneuploidy, chromothripsis, and other forms of chromosomal instability (CIN), yet how this occurs remains unclear. A well-established mechanism of CIN is the overproduction of centrosomes, which promotes tumorigenesis in various mouse models. Therefore, we developed a single-cell assay for quantifying centrosomes in human prostate tissue. Surprisingly, centrosome loss-which has not been described in human cancer-was associated with PCa progression. By chemically or genetically inducing centrosome loss in nontumorigenic prostate epithelial cells, mitotic errors ensued, producing aneuploid, and multinucleated cells. Strikingly, transient or chronic centrosome loss transformed prostate epithelial cells, which produced highly proliferative and poorly differentiated malignant tumors in mice. Our findings suggest that centrosome loss could create a cellular crisis with oncogenic potential in prostate epithelial cells.
Note6 month embargo; published online: 2 September 2019
VersionFinal accepted manuscript
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