NDR1 enhances USP9X-mediated AR deubiquitination and promotes enzalutamide resistance in castration-resistant prostate cancer.

ABSTRACT: Castration-resistant prostate cancer (CRPC) enzalutamide resistance is a significant issue in the current treatment of prostate cancer (PCa). Previously, nuclear Dbf2-related 1 (NDR1) was found to influence metastasis in PCa patients; however, the role of NDR1 in enzalutamide resistance in CRPC remains unclear. In this study, we found that after CRPC cells developed resistance to enzalutamide, NDR1 expression levels were elevated and that NDR1 expression could reduce the sensitivity of CRPC cells to enzalutamide. Furthermore, in androgen receptor (AR) positive PCa cell lines, the use of enzalutamide induced an increase in NDR1 expression levels. Further mechanistic exploration revealed that NDR1 positively regulates AR protein expression levels by promoting the deubiquitination of AR by US

SUBMITTER: Zheng Z 

PROVIDER: S-EPMC12509700 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature