ATF4 suppresses hepatocarcinogenesis by inducing SLC7A11 (xCT) to block stress-related ferroptosis.

ABSTRACT:

Background & aims

Hepatocellular carcinoma (HCC), a leading cause of cancer-related death, is associated with viral hepatitis, non-alcoholic steatohepatitis (NASH), and alcohol-related steatohepatitis, all of which trigger endoplasmic reticulum (ER) stress, hepatocyte death, inflammation, and compensatory proliferation. Using ER stress-prone MUP-uPA mice, we established that ER stress and hypernutrition cooperate to cause NASH and HCC, but the contribution of individual stress effectors, such as activating transcription factor 4 (ATF4), to HCC and their underlying mechanisms of action remained unknown.

Methods

Hepatocyte-specific ATF4-deficient MUP-uPA mice (MUP-uPA/Atf4^Δhep) and control MUP-uPA/Atf4^F/F mice were fed a high-fat diet to induce NASH-relat

SUBMITTER: He F 

PROVIDER: S-EPMC11332364 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature