癌细胞
细胞生物学
原癌基因酪氨酸蛋白激酶Src
癌症
癌症研究
受体
辅活化剂
细胞生长
核受体辅活化子3
活性氧
生物
信号转导
生物化学
转录因子
遗传学
基因
作者
Lei Wang,Yang Yu,Dar Chone Chow,Fei Yan,Chih Chao Hsu,Fabio Stossi,Michael A. Mancini,Timothy Palzkill,Lan Liao,Suoling Zhou,Jianming Xu,David M. Lonard,Bert W. O’Malley
出处
期刊:Cancer Cell
[Elsevier]
日期:2015-08-01
卷期号:28 (2): 240-252
被引量:66
标识
DOI:10.1016/j.ccell.2015.07.005
摘要
By integrating growth pathways on which cancer cells rely, steroid receptor coactivators (SRC-1, SRC-2, and SRC-3) represent emerging targets in cancer therapeutics. High-throughput screening for SRC small molecule inhibitors (SMIs) uncovered MCB-613 as a potent SRC small molecule "stimulator" (SMS). We demonstrate that MCB-613 can super-stimulate SRCs' transcriptional activity. Further investigation revealed that MCB-613 increases SRCs' interactions with other coactivators and markedly induces ER stress coupled to the generation of reactive oxygen species (ROS). Because cancer cells overexpress SRCs and rely on them for growth, we show that we can exploit MCB-613 to selectively induce excessive stress in cancer cells. This suggests that over-stimulating the SRC oncogenic program can be an effective strategy to kill cancer cells.
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