Hepatocyte TM4SF5-mediated cytosolic NCOA3 stabilization and macropinocytosis support albumin uptake and bioenergetics for hepatocellular carcinoma progression.

ABSTRACT: Transmembrane 4 L six family member 5 (TM4SF5) is involved in hepatocellular carcinoma (HCC) development and progression. Although TM4SF5 also promotes migration and invasion, it remains unclear how the metabolic context affects metastatic potential. Here we explored how TM4SF5 affects albumin uptake for HCC progression using TM4SF5 knockout or reintroduced hepatocyte and animal systems. Serum-deprived hepatocytes formed filopodia-like processes depending on TM4SF5 expression, which was altered by albumin replenishment for membranous PIP₃-dependent macropinocytosis. Macropinocytosis required nuclear receptor coactivator 3 (NCOA3) stabilized in the cytosol and PTEN inactivation via binding to TM4SF5_WT. TM4SF5-mediated albumin uptake led to ATP-linked respiration and ce

SUBMITTER: Lee H 

PROVIDER: S-EPMC12046047 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature