CEP55 is a determinant of cell fate during perturbed mitosis in breast cancer

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 a...

Descripción completa

Detalles Bibliográficos
Autores principales: Kalimutho, Murugan, Sinha, Debottam, Jeffery, Jessie, Nones, Katia, Srihari, Sriganesh, Fernando, Winnie C, Duijf, Pascal HG, Vennin, Claire, Raninga, Prahlad, Nanayakkara, Devathri, Mittal, Deepak, Saunus, Jodi M, Lakhani, Sunil R, López, J Alejandro, Spring, Kevin J, Timpson, Paul, Gabrielli, Brian, Waddell, Nicola, Khanna, Kum Kum
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Research Articles
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127888/
https://www.ncbi.nlm.nih.gov/pubmed/30108112
http://dx.doi.org/10.15252/emmm.201708566
Descripción
Sumario: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.

Ejemplares similares