GUTK induces apoptosis in reactivating quiescent prostate cancer cells via Aurora A-mediated stabilization of SOD2

Hu, selectively eradicates reactivating quiescent PCa cells by inducing mitochondrial apoptosis through caspase activation and loss of mitochondrial membrane potential (ΔΨm). Mechanistically, GUTK suppresses Aurora A recovery and stabilizes SOD2 protein, thereby promoting mitochondrial dysfunction and apoptosis. SOD2 enhances, whereas Aurora A overexpression attenuates, GUTK-induced cell death. In orthotopic and xenograft prostate tumor models, GUTK combined with docetaxel significantly inhibits tumor growth and suppresses post-chemotherapy recurrence without evident toxicity. These findings identify GUTK as a potential therapeutic agent targeting reactivating quiescent PCa cells and highlight the Aurora A-SOD2 axis as a promising pathway for preventing PCa recurrence.