Glucocorticoid Receptor Regulates and Interacts with LEDGF/p75 to Promote Docetaxel Resistance in Prostate Cancer Cells

Patients with advanced prostate cancer (PCa) invariably develop resistance to anti-androgen therapy and taxane-based chemotherapy. Glucocorticoid receptor (GR) has been implicated in PCa resistance; however, the mechanisms underlying GR-mediated chemoresistance remain unclear. Lens epithelium-derived growth factor p75 (LEDGF/p75, also known as PSIP1 DFS70) is a glucocorticoid-induced transcription co-activator chemoresistance. We investigated contribution of GR–LEDGF/p75 axis docetaxel (DTX)-resistance cells. GR silencing DTX-sensitive -resistant cells decreased LEDGF/p75 expression, upregulation enzalutamide-resistant correlated increased expression. ChIP-sequencing revealed binding sites promoter. STRING protein–protein interaction analysis indicated that belong same transcriptional network, immunochemical studies demonstrated their co-immunoprecipitation co-localization DTX-resistant The modulators exicorilant relacorilant sensitivity chemoresistant DTX-induced cell death, this effect was more pronounced upon silencing. RNA-sequencing or knockdown transcriptomic overlap targeting signaling pathways associated survival proliferation, cancer, resistance. These implicate provide pre-clinical rationale for developing novel therapeutic strategies PCa.