SLC7A11 upregulation via AR and NEDD4L ubiquitination contributes to ferroptosis inhibition and enzalutamide resistance in castration-resistant prostate cancer.

ABSTRACT: Advanced prostate cancer (PCa) is associated with a poor prognosis, particularly in patients who progress to castration-resistant prostate cancer (CRPC). The emergence of enzalutamide (Enz), a second-generation androgen receptor inhibitor, has effectively extended the median survival of these patients. However, drug resistance frequently develops during clinical use. Multiple studies have suggested that ferroptosis inducers can reverse cancer resistance to Enz, though the exact mechanisms remain unclear. In this study, we found that CRPC cells exhibit a concentration-dependent decrease in ferroptosis in response to Enz. This change is attributed to the upregulation of the protein level of SLC7A11. Protein stability assays and database analyses showed that SLC7A11 undergoes post-translation

SUBMITTER: Tang M 

PROVIDER: S-EPMC12325610 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature