CEP 55 is a determinant of cell fate during perturbed mitosis in breast cancer

  • Kalimutho M
  • Sinha D
  • Jeffery J
  • et al.
59Citations
Citations of this article
41Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

The centrosomal protein, CEP55, is a key regulator of cytokinesis, and its overexpression is linked to genomic instability, a hallmark of cancer. However, the mechanism by which it mediates genomic instability remains elusive. Here, we showed that CEP55 overexpression/knockdown impacts survival of aneuploid cells. Loss of CEP55 sensitizes breast cancer cells to anti-mitotic agents through premature CDK1/cyclin B activation and CDK1 caspase-dependent mitotic cell death. Further, we showed that CEP55 is a downstream effector of the MEK1/2-MYC axis. Blocking MEK1/2-PLK1 signaling therefore reduced outgrowth of basal-like syngeneic and human breast tumors in in vivo models. In conclusion, high CEP55 levels dictate cell fate during perturbed mitosis. Forced mitotic cell death by blocking MEK1/2-PLK1 represents a potential therapeutic strategy for MYC-CEP55-dependent basal-like, triple-negative breast cancers.

Cite

CITATION STYLE

APA

Kalimutho, M., Sinha, D., Jeffery, J., Nones, K., Srihari, S., Fernando, W. C., … Khanna, K. K. (2018). CEP 55 is a determinant of cell fate during perturbed mitosis in breast cancer. EMBO Molecular Medicine, 10(9). https://doi.org/10.15252/emmm.201708566

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free