ATF3-SLC7A7 Axis Regulates mTORC1 Signaling to Suppress Lipogenesis and Tumorigenesis in Hepatocellular Carcinoma.

ABSTRACT: Hepatocellular carcinoma (HCC) poses a substantial global health burden, with poor prognosis and high mortality rates. Dysregulated lipid metabolism has emerged as a critical driver of HCC progression. While mTORC1 signaling is known to promote lipid synthesis in HCC, the regulatory mechanisms governing mTORC1 remain largely unclear. Here, we demonstrate that mTORC1 inhibition significantly reduces lipogenesis in HCC and uncover a regulatory axis involving the transcription factor ATF3 and the leucine-arginine transporter SLC7A7. Transcriptomic analysis of HCC patients reveals an inverse correlation between ATF3 expression and lipid synthesis, a finding corroborated by experimental validation. Mechanistically, ATF3 suppresses mTORC1 signaling, thereby inhibiting lipid biosynthesis, with SL

SUBMITTER: Zhang Q 

PROVIDER: S-EPMC11854064 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature