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
相关论文
共 50 条
  • [41] REC8 inhibits proliferation, migration and invasion of breast cancer cells by targeting CDC20
    He, Shaodan
    Liu, Danping
    Chen, Zhuanhong
    MOLECULAR MEDICINE REPORTS, 2022, 26 (01)
  • [42] A rapid assay for drug sensitivity of glioblastoma stem cells
    Gal, Hilah
    Makovitzki, Arik
    Amariglio, Ninette
    Rechavi, Gideon
    Ram, Zvi
    Givol, David
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2007, 358 (03) : 908 - 913
  • [43] Cdc20 overexpression is involved in temozolomide-resistant glioma cells with epithelial-mesenchymal transition
    Wang, Jianjiao
    Zhou, Fenggang
    Li, Yang
    Li, Qingsong
    Wu, Zhichao
    Yu, Lili
    Yuan, Fei
    Liu, Jie
    Tian, Yu
    Cao, Yu
    Zhao, Yan
    Zheng, Yongri
    CELL CYCLE, 2017, 16 (24) : 2355 - 2365
  • [44] Rottlerin inhibits cell growth and invasion via down-regulation of Cdc20 in glioma cells
    Wang, Lixia
    Hou, Yingying
    Yin, Xuyuan
    Su, Jingna
    Zhao, Zhe
    Ye, Xiantao
    Zhou, Xiuxia
    Zhou, Li
    Wang, Zhiwei
    ONCOTARGET, 2016, 7 (43) : 69770 - 69782
  • [45] MYBL2 in synergy with CDC20 promotes the proliferation and inhibits apoptosis of gastric cancer cells
    Deng, Qianxi
    Wu, Linju
    Li, Yiming
    Zou, Long
    ADVANCES IN CLINICAL AND EXPERIMENTAL MEDICINE, 2021, 30 (09): : 957 - 966
  • [46] Notch signaling regulates metabolic heterogeneity in glioblastoma stem cells
    Bayin, N. Sumru
    Frenster, Joshua D.
    Sen, Rajeev
    Si, Sheng
    Modrek, Aram S.
    Galifianakis, Nataliya
    Dolgalev, Igor
    Ortenzi, Valerio
    Illa-Bochaca, Irineu
    Khahera, Anadjeet
    Serrano, Jonathan
    Chiriboga, Luis
    Zagzag, David
    Golfinos, John G.
    Doyle, Werner
    Tsirigos, Aristotelis
    Heguy, Adriana
    Chesler, Mitch
    Barcellos-Hoff, Mary Helen
    Snuderl, Matija
    Placantonakis, Dimitris G.
    ONCOTARGET, 2017, 8 (39) : 64932 - 64953
  • [47] A CDC20-APC/SOX2 signaling pathway controls human glioblastoma stem-like cells
    Kim, Albert H.
    Mao, Diane
    Gujar, Amit
    Mahlokozera, Tatenda
    Chen, Ishita
    Pan, Yanchun
    Yano, Hiroko
    JOURNAL OF NEURO-ONCOLOGY, 2015, 122 (03) : 617 - 617
  • [48] PERK Regulates Glioblastoma Sensitivity to ER Stress Although Promoting Radiation Resistance
    Dadey, David Y. A.
    Kapoor, Vaishali
    Khudanyan, Arpine
    Thotala, Dinesh
    Hallahan, Dennis E.
    MOLECULAR CANCER RESEARCH, 2018, 16 (10) : 1447 - 1453
  • [49] Radiation-induced glioblastoma signaling cascade regulates viability, apoptosis and differentiation of neural stem cells (NSC)
    Ivanov, Vladimir N.
    Hei, Tom K.
    APOPTOSIS, 2014, 19 (12) : 1736 - 1754
  • [50] Radiation-induced glioblastoma signaling cascade regulates viability, apoptosis and differentiation of neural stem cells (NSC)
    Vladimir N. Ivanov
    Tom K. Hei
    Apoptosis, 2014, 19 : 1736 - 1754