Role of C-Terminal Binding Protein as Oncogene and Therapeutic Target in Epithelial Ovarian Cancer
Abstract
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) 4/5. CtBP knockdown upregulated DR4/5, and triggered autonomous apoptosis via caspase 8 activation. We further demonstrated that CtBP represses DR4 or/and DR5 in different cell-type contexts. Activation of DR4/5 by CtBP loss sensitized cell susceptibility to TRAIL. CtBP binds at the promoter regions of DR4/5, represses DR4/5 expression, presumably through the recruitment to a regulatory complex. We also found that CtBP1 and CtBP2 coordinate to repress the DR4/5 pro-apoptotic receptors. Collectively, this study identifies CtBP as a potent suppressor of DR4/5 and indicates targeting CtBP as a promising therapeutic strategy for HGSOC.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2019
- Accession Number
- AD1087679
Entities
People
- Boxiao Ding
- Jolene Windle
- Steven R. Grossman
- Yuan Fang
Organizations
- Virginia Commonwealth University