Hippo-mediated suppression of IRS2/AKT signaling prevents hepatic steatosis and liver cancer.

ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is a major risk factor for liver cancer; therefore, its prevention is an important clinical goal. Ablation of phosphatase and tensin homolog (PTEN) or the protein kinase Hippo signaling pathway induces liver cancer via activation of AKT or the transcriptional regulators YAP/TAZ, respectively; however, the potential for crosstalk between the PTEN/AKT and Hippo/YAP/TAZ pathways in liver tumorigenesis has thus far remained unclear. Here, we have shown that deletion of both PTEN and SAV1 in the liver accelerates the development of NAFLD and liver cancer in mice. At the molecular level, activation of YAP/TAZ in the liver of Pten-/- Sav1-/- mice amplified AKT signaling through the upregulation of insulin receptor substrate 2 (IRS2) expression. Both ablati

SUBMITTER: Jeong SH 

PROVIDER: S-EPMC5824861 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature