GFAT1 promotes the progression of hepatocellular carcinoma via enhancing the O-GlcNAcylation of VEZF1.

ABSTRACT: Glutamine-fructose-6-phosphate amidotransferase 1 (GFAT1), the first rate-limiting enzyme in the hexosamine biosynthetic pathway (HBP), is a pivotal regulator of HBP flux. Despite its established significance, the molecular underpinnings of GFAT1's role in hepatocellular carcinoma (HCC) remain to be elucidated. Here, we found that GFAT1 was upregulated in HCC, and high GFAT1 level was correlated with poor patient prognosis. Our in vitro and in vivo studies demonstrated that GFAT1 facilitated hepatoma cell proliferation and invasion by enhancing HBP and O-GlcNAcylation through its enzymatic activity. Global profiling of O-GlcNAcylation identified vascular endothelial zinc finger protein 1 (VEZF1) as a key substrate heavily O-GlcNAcylated in GFAT1-overexpressing hepatoma cells. Notably, O-Gl

SUBMITTER: Yang JY 

PROVIDER: S-EPMC12381164 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature