Interactions between driver genes shape the signaling pathway landscape and direct hepatocellular carcinoma therapy.

ABSTRACT: Hepatocellular carcinoma (HCC) is one of the most lethal malignancies, whose initiation and development are driven by alterations in driver genes. In this study, we identified four driver genes (TP53, PTEN, CTNNB1, and KRAS) that show a high frequency of somatic mutations or copy number variations (CNVs) in patients with HCC. Four different spontaneous HCC mouse models were constructed to screen for changes in various kinase signaling pathways. The sgTrp53 + sgPten tumor upregulated mTOR and noncanonical nuclear factor-κB signaling, which was shown to be strongly inhibited by rapamycin (an mTOR inhibitor) in vitro and in vivo. The JAK-signal transducer and activator of transcription (STAT) signaling was activated in Ctnnb1^mut  + sgPten tumor, the proliferation of which was stron

SUBMITTER: Shen Y 

PROVIDER: S-EPMC10236629 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature