生物
基因敲除
基诺美
基因沉默
神经干细胞
RNA干扰
癌症研究
干细胞
细胞分化
细胞周期
调节器
细胞
信号转导
细胞生物学
细胞凋亡
遗传学
基因
核糖核酸
作者
Heiko Wurdak,Shoutian Zhu,Angélica Romero,Mihaela Lorger,James P. Watson,Chih yuan Chiang,Jay Zhang,Vanita Natu,Luke L. Lairson,John R. Walker,Christopher Trussell,Griffith R. Harsh,Hannes Vogel,Brunhilde Felding-Habermann,Anthony P. Orth,Loren Miraglia,Daniel R. Rines,Stephen Skirboll,Peter G. Schultz
出处
期刊:Cell Stem Cell
[Elsevier]
日期:2010-01-01
卷期号:6 (1): 37-47
被引量:119
标识
DOI:10.1016/j.stem.2009.11.002
摘要
Glioblastoma multiforme (GBM) is a highly aggressive form of brain cancer associated with a very poor prognosis. Recently, the initiation and growth of GBM has been linked to brain tumor-initiating cells (BTICs), which are poorly differentiated and share features with neural stem cells (NSCs). Here we describe a kinome-wide RNA interference screen to identify factors that control the tumorigenicity of BTICs. We identified several genes whose silencing induces differentiation of BTICs derived from multiple GBM patients. In particular, knockdown of the adaptor protein TRRAP significantly increased differentiation of cultured BTICs, sensitized the cells to apoptotic stimuli, and negatively affected cell cycle progression. TRRAP knockdown also significantly suppressed tumor formation upon intracranial BTIC implantation into mice. Together, these findings support a critical role for TRRAP in maintaining a tumorigenic, stem cell-like state.
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