PI3Kγ promotes obesity-associated hepatocellular carcinoma by regulating metabolism and inflammation.

ABSTRACT:

Background & aims

Phosphatidylinositides-3 kinases (PI3Ks) are promising drug targets for cancer therapy, but blockage of PI3K-AKT signalling causes hyperglycaemia, hyperinsulinaemia, and liver damage in patients, and hepatocellular carcinoma (HCC) in mice. There are 4 PI3Ks: PI3Kα, PI3Kβ, PI3Kδ, and PI3Kγ. The role of PI3Kγ in HCC is unknown.

Methods

We performed histopathological, metabolic, and molecular phenotyping of mice with genetic ablation of PI3Kγ using models where HCC was initiated by the carcinogen diethylnitrosamine (DEN) and promoted by dietary or genetic obesity (ob/ob). The role of PI3Kγ in leucocytes was investigated in mice lacking PI3Kγ in haematopoietic and endothelial cells.

Results

Loss of PI3Kγ had no effects on the development of DEN-induced H

SUBMITTER: Becattini B 

PROVIDER: S-EPMC8521290 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature