Targeting endoplasmic reticulum stress and nitroso-redox imbalance in neuroendocrine prostate cancer: the therapeutic role of nitric oxide.

ABSTRACT: Neuroendocrine prostate cancer (NEPC) is an aggressive and therapy-resistant subtype of prostate cancer characterized by high levels of endoplasmic reticulum (ER) stress and metabolic dysregulation. The subsequential metabolic adaptations in the cancer cells reinforce survival mechanisms that contribute to therapy resistance and metastasis. The oncogenic driver neuroblastoma-derived MYC (MYCN) exacerbates ER stress by increasing calcium ion efflux from the ER into mitochondria, promoting glycolytic and oxidative stress. Here, we demonstrate that nitric oxide (NO) signaling is dysregulated in NEPC, thus allowing impaired S-nitrosylation of MYCN and uncontrolled ER stress. We show that exogenous NO supplementation restores MYCN S-nitrosylation at Cys4, Cys186, and Cys464. This re-establishme

SUBMITTER: Firdaus F 

PROVIDER: S-EPMC12592524 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature