CDC20 regulates sensitivity to chemotherapy and radiation in glioblastoma stem cells

Author:

Mao Diane D.,Cleary Ryan T.,Gujar AmitORCID,Mahlokozera Tatenda,Kim Albert H.

Abstract

Glioblastoma stem cells (GSCs) are an important subpopulation in glioblastoma, implicated in tumor growth, tumor recurrence, and radiation resistance. Understanding the cellular mechanisms for chemo- and radiation resistance could lead to the development of new therapeutic strategies. Here, we demonstrate that CDC20 promotes resistance to chemotherapy and radiation therapy. CDC20 knockdown does not increase TMZ- and radiation-induced DNA damage, or alter DNA damage repair, but rather promotes cell death through accumulation of the pro-apoptotic protein, Bim. Our results identify a CDC20 signaling pathway that regulates chemo- and radiosensitivity in GSCs, with the potential for CDC20-targeted therapeutic strategies in the treatment of glioblastoma.

Funder

National Institutes of Health

Christopher Davidson and Knight Family Fund

Alvin J. Siteman Cancer Center

Duesenberg Research Fund

Publisher

Public Library of Science (PLoS)

Subject

Multidisciplinary

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