GNL3 Orchestrates AR Transcriptional Programs to Drive Castration-Resistant Prostate Cancer and Immune Evasion - PubMed
8 hours ago
- #immune evasion
- #transcriptional regulation
- #prostate cancer
- GNL3 is identified as a novel AR coregulator in castration-resistant prostate cancer (CRPC).
- GNL3 physically interacts with AR, enhancing its chromatin occupancy and coactivating transcriptional programs that promote cell proliferation (e.g., NEK2, CDC20).
- GNL3 also functions as a corepressor of immune-responsive genes (e.g., CXCL10, TAP1) via class I HDACs, facilitating CD8+ T cell elimination and immunosuppression.
- GNL3 expression and AR-GNL3 complex formation increase from normal prostate to CRPC and correlate with poor clinical outcomes.
- GNL3 knockdown sensitizes CRPC cells to AR antagonists and impairs tumor growth and metastasis.
- Combinatorial inhibition of NEK2, class I HDACs, and AR signaling is proposed as a potential therapeutic strategy for CRPC.