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.
CITATION STYLE
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
Mendeley helps you to discover research relevant for your work.