Role of C-Terminal Binding Protein as Oncogene and Therapeutic Target in Epithelial Ovarian Cancer
Technical Report,01 May 2018,30 Apr 2019
Virginia Commonwealth University Richmond United States
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The C-terminal binding protein CtBP is elevated in epithelial ovarian cancer, especially in high-grade serous ovarian cancer HGSOC and has been implicated in cancer malignancy. However, the CtBP dependency in HGSOC is not well documented. Here we report that CtBP represses HGSOC apoptosis through death receptors DRs 45. CtBP knockdown upregulated DR45, and triggered autonomous apoptosis via caspase 8 activation. We further demonstrated that CtBP represses DR4 orand DR5 in different cell-type contexts. Activation of DR45 by CtBP loss sensitized cell susceptibility to TRAIL. CtBP binds at the promoter regions of DR45, represses DR45 expression, presumably through the recruitment to a regulatory complex. We also found that CtBP1 and CtBP2 coordinate to repress the DR45 pro-apoptotic receptors. Collectively, this study identifies CtBP as a potent suppressor of DR45 and indicates targeting CtBP as a promising therapeutic strategy for HGSOC.
- Medicine and Medical Research