AFP-HSP90 mediated MYC/MET activation promotes tumor progression in hepatocellular carcinoma and gastric cancers.

ABSTRACT: Alpha-fetoprotein (AFP) elevation is a well-known biomarker in various diseases, particularly in the diagnosis of hepatocellular carcinoma (HCC). Intracellular AFP has been previously implicated in promoting tumorigenesis. In this study, we discovered that AFP enhances the stability of oncoproteins c-MYC and c-MET, thereby facilitating the progression of liver and gastric tumors. Our findings suggest that AFP acts by stabilizing these oncoproteins, which are clients of heat shock protein 90 (HSP90), and prevents their degradation through ubiquitination. Intriguingly, we identified AFP as a novel co-chaperone of HSP90, demonstrating its ability to regulate the stabilization of HSP90 client proteins. Furthermore, our results indicate that inhibiting AFP or HSP90 enhances the cytotoxicity of

SUBMITTER: Lin Z 

PROVIDER: S-EPMC11321088 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature