TY - JOUR
T1 - CDC20 regulates sensitivity to chemotherapy and radiation in glioblastoma stem cells
AU - Mao, Diane D.
AU - Cleary, Ryan T.
AU - Gujar, Amit
AU - Mahlokozera, Tatenda
AU - Kim, Albert H.
N1 - Funding Information:
This work was supported by National Institutes of Health (www.nih.gov) grant R01 NS094670 (to A.H.K.); the Duesenberg Research Fund (to A.H.K.), and the Christopher Davidson and Knight Family Fund (to A.H.K.). This work was also supported by the Alvin J. Siteman Cancer Center Investment Program from The Foundation for Barnes-Jewish Hospital and the Barnard Trust. We would like to thank members of the AHK and HY laboratories for thoughtful discussion and technical assistance.
Publisher Copyright:
Copyright: © 2022 Mao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2022/6
Y1 - 2022/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85132534871&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0270251
DO - 10.1371/journal.pone.0270251
M3 - Article
C2 - 35737702
AN - SCOPUS:85132534871
SN - 1932-6203
VL - 17
JO - PloS one
JF - PloS one
IS - 6 Jun
M1 - e0270251
ER -