AKR1C3-PKM2-oxidative phosphorylation axis drives prostate cancer radioresistance via UBE2T upregulation - PubMed
4 hours ago
- #Radioresistance
- #Prostate Cancer
- #AKR1C3
- AKR1C3 identified as a key target in prostate cancer radioresistance through bioinformatic analysis of TCGA and GEO data.
- AKR1C3 promotes radioresistance in both AR-positive and AR-negative prostate cancer cells, validated in vivo and in vitro.
- AKR1C3 binds to PKM2, accelerating its degradation, which inhibits glycolysis and enhances oxidative phosphorylation (OXPHOS).
- Increased OXPHOS boosts ROS production, promoting NRF2 nuclear translocation and activating transcription of DNA repair protein UBE2T.
- Enhanced DNA damage repair via UBE2T upregulation leads to greater radiotherapy resistance in prostate cancer cells with high AKR1C3 expression.
- Targeting AKR1C3 shows potential for overcoming radioresistance, offering novel insights for clinical prostate cancer treatment.