期刊
ONCOGENE
卷 32, 期 40, 页码 4727-4736出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2012.616
关键词
whole-chromosome instability; aneuploidy; cancer biology; oncogene-induced mitotic stress; non-cell autonomous; tumor microenvironment
资金
- Young Investigator Award from Alex's Lemonade Stand Foundation
- Breast Cancer Research Foundation
One form of chromosome instability (CIN), the recurrent missegregation of whole chromosomes during cell division (W-CIN), leads to aneuploidy. Although W-CIN is a hallmark of most cancers, mutations in genes involved in chromosome segregation are exceedingly rare. We discuss an oncogene-induced mitotic stress model that provides a mechanistic framework to explain this paradox. We also review the tumor-promoting and tumor-suppressing consequences of W-CIN. Importantly, we do this in the context of cancer as a complex systemic disease, rather than as a simple linearly progressing disorder that arises from a single abnormal cell population. Accordingly, we highlight the often neglected effects of W-CIN on key non-cell-autonomous entities, such as the immune system and the tumor microenvironment. Distinct tissue-specific susceptibilities to W-CIN-induced tumorigenesis and the clinical implications of W-CIN are also discussed.
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