IGF2BP1-HAX-1 positive feedback loop-mediated HAX-1 overexpression blocks autophagic flux and promotes chemoresistance in nasopharyngeal carcinoma.

ABSTRACT: Autophagy is associated with chemoresistance, which is the leading cause of failure in chemotherapeutic treatments. Among the various aspects of autophagy, autophagic flux serves as a critical indicator for evaluating the dynamic processes involved.We report herein that the multifunctional protein HAX-1 promotes chemoresistance by effectively blocking the fusion of autophagosomes with lysosomes. Complementary mass spectrometric and functional studies also demonstrated that HAX-1 recruits NEDD4 to promote Rab7a degradation and inhibits binding of Rab7a with SNAREs by competitively binding to it. Furthermore, HAX-1 binds IGF2BP1 mRNA, thereby contributing to its stability and translation. Moreover, IGF2BP1 enhanced HAX-1 m6A methylation, thereby enhancing its stability. By way of in-vivo and

SUBMITTER: Zhang S 

PROVIDER: S-EPMC11889316 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature