PDHA1-acetylation signaling suppresses cuproptosis to attenuate anti-androgen effect in prostate cancer - PubMed
4 hours ago
- #cuproptosis
- #prostate cancer
- #enzalutamide resistance
- PDHA1-acetylation signaling suppresses cuproptosis, contributing to enzalutamide (Enz) resistance in castration-resistant prostate cancer (CRPC).
- PDHA1 increases acetyl-CoA, enhancing histone H3K27 acetylation and upregulating SLC7A11, which promotes cysteine uptake and glutathione (GSH) synthesis.
- Elevated GSH chelates intracellular copper, suppressing cuproptosis and reducing Enz efficacy.
- Targeting PDHA1 restores cuproptosis and sensitizes CRPC cells to Enz treatment, offering a potential therapeutic strategy.
- The study highlights PDHA1 inhibition as a promising approach to counteract Enz resistance in refractory prostate cancer.