GSE116005
ERa-CtBP-mediated repression of Homologous-recombination repair in ovarian cancer improves chemo-sensitivity [ChIP-seq]
Deficiency in homologous recombination repair (HRR) is frequently associated with hormone-responsive cancers. Epithelial ovarian cancer (EOC) is a typical hormone-related tumor, with defects of HRR in up to half of cases. However, whether there are molecular connections between estrogen signaling and HRR deficiency in EOC remains unknown. Here we report an inverse correlation between estrogen signaling and HRR activity in EOC. Genome-wide mapping of ERa reveals ERa co-bindings with co-repressor CtBP, especially on many HRR gene loci, in EOC cells but not in breast cancer cells. Consistently, depleting ERa in EOC cells up-regulates HRR activity and HRR gene expression. Importantly, estrogen signaling enhances the sensitivity of ovarian cancer cells to chemotherapy agents in vitro and in vivo. Large-scale analyses further indicate that estrogen replacement and ERa expression are associated with favorable survival of EOC patients. These findings characterize a novel role of ERa in mediating the molecular connection between hormone and HRR in EOC, and suggest that estrogen signaling may improve the treatment outcome of EOC patients. Overall design: ChIPSeq of SKOV3 cells. Samples including Input, anti-CtBP, anti-ERa and anti-CtBP treated with Fulverstrant.