Gankyrin drives malignant transformation of chronic liver damage-mediated fibrosis via the Rac1/JNK pathway.

ABSTRACT: Hepatocarcinogenesis is a complex process involving chronic liver injury, inflammation, unregulated wound healing, subsequent fibrosis and carcinogenesis. To decipher the molecular mechanism underlying transition from chronic liver injury to dysplasia, we investigated the oncogenic role of gankyrin (PSMD10 or p28GANK) during malignant transformation in a transgenic mouse model. Here, we find that gankyrin increased in patients with cirrhosis. In addition to more severe liver fibrosis and tumorigenesis after DEN plus CCl4 treatment, hepatocyte-specific gankyrin-overexpressing mice (gankyrinhep) exhibited malignant transformation from liver fibrosis to tumors even under single CCl4 administration, whereas wild-type mice merely experienced fibrosis. Consistently, enhanced hepatic injury, seve

SUBMITTER: Zhao X 

PROVIDER: S-EPMC4669699 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature