Abstract
The mitotic spindle is the bipolar, microtubule-based structure that segregates chromosomes at each cell division. Aberrant spindles are frequently observed in cancer cells, but how oncogenic transformation affects spindle mechanics and function, particularly in the mechanical context of solid tumors, remains poorly understood. Here, we constitutively overexpress the oncogene cyclin D1 in human MCF10A cells to probe its effects on spindle architecture and response to compressive force. We find that cyclin D1 overexpression increases the incidence of spindles with extra poles, centrioles, and chromosomes. However, it also protects spindle poles from fracturing under compressive force, a deleterious outcome linked to multipolar cell divisions. Our findings suggest that cyclin D1 overexpression may adapt cells to increased compressive stress, possibly contributing to its prevalence in cancers such as breast cancer by allowing continued proliferation in mechanically challenging environments.
Funder
Fannie and John Hertz Foundation Fellowship
National Science Foundation
UCSF Discovery Fellows Program
National Institute of General Medical Sciences
Chan Zuckerberg Initiative
UCSF Byers Award
Mark Foundation For Cancer Research
Atwater Family Foundation
National Institutes of Health
Congressionally Directed Medical Research Programs
Publisher
Public Library of Science (PLoS)