The oncogene cyclin D1 promotes bipolar spindle integrity under compressive force

Author:

Sutanto RenaldoORCID,Neahring LilaORCID,Serra Marques Andrea,Jacobo Jacobo Mauricio,Kilinc Seda,Goga Andrei,Dumont SophieORCID

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)

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