Histone methyltransferase KMT2D promotes castration-resistant prostate cancer progression by reactivating AR through FOXA1 - PubMed
4 hours ago
- #AR signaling
- #Castration-resistant prostate cancer
- #KMT2D
- KMT2D is identified as a critical epigenetic oncogene in prostate cancer (PCa), with elevated expression linked to poor prognosis.
- KMT2D promotes castration-resistant prostate cancer (CRPC) progression by reactivating androgen receptor (AR) signaling through recruitment of FOXA1 to AR-specific enhancers, enhancing chromatin accessibility.
- FOXA1 mutations disrupt the KMT2D-FOXA1 regulatory interplay, highlighting their functional connection in AR activation.
- The KMT2D-FOXA1-AR axis regulates ketone body metabolism by controlling HMGCS2 transcription, which supports tumor growth.
- Pharmacological inhibition of UTX, a demethylase in the COMPASS complex essential for KMT2D, reduces H3K4me1 deposition and suppresses AR signaling and tumor proliferation.
- UTX inhibition is proposed as a promising therapeutic strategy to target KMT2D-driven AR-dependent progression in PCa.