P53R245W Mutation Fuels Cancer Initiation and Metastases in NASH-driven Liver Tumorigenesis.

ABSTRACT: Obesity is a significant global health concern. Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NASH) are common risk factors for hepatocellular carcinoma (HCC) and are closely associated with metabolic comorbidities, including obesity and diabetes. The TP53 tumor suppressor is the most frequently mutated gene in liver cancers, with half of these alterations being missense mutations. These mutations produce highly abundant proteins in cancer cells which have both inhibitory effects on wildtype (WT) p53, and gain-of-function (GOF) activities that contribute to tumor progression. A Western diet increases p53 activity in the liver. To elucidate the functional consequences of Trp53 mutations in a NASH-driven liver tumorigenesis model, we generated somatic mouse models with

SUBMITTER: Dibra D 

PROVIDER: S-EPMC10761659 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature