CDC20 regulates sensitivity to chemotherapy and radiation in glioblastoma stem cells

被引:5
|
作者
Mao, Diane D. [1 ]
Cleary, Ryan T. [2 ]
Gujar, Amit [3 ]
Mahlokozera, Tatenda [1 ]
Kim, Albert H. [1 ,4 ]
机构
[1] Washington Univ, Dept Neurol Surg, Sch Med, St Louis, MO 63110 USA
[2] St Louis Univ, Dept Neurol Surg, Sch Med, St Louis, MO USA
[3] Jackson Lab Genom Med, Farmington, CT USA
[4] Washington Univ, Sch Med, Brain Tumor Ctr, Siteman Canc Ctr, St Louis, MO 63110 USA
来源
PLOS ONE | 2022年 / 17卷 / 06期
基金
美国国家卫生研究院;
关键词
DNA-DAMAGE RESPONSE; SIGNALING PATHWAY; RADIORESISTANCE; TEMOZOLOMIDE; CHECKPOINTS; INHIBITION; ABROGATION;
D O I
10.1371/journal.pone.0270251
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页数:14
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