Disrupting CCDC137-mediated LZTS2 and β-TrCP interaction in the nucleus inhibits hepatocellular carcinoma development via β-catenin and AKT.

ABSTRACT: Hepatocellular carcinoma (HCC) is a highly heterogeneous solid tumor, with its biological characteristics intricately linked to the activation of oncogenes. This research specifically explored CCDC137, a molecule within the CCDC family exhibiting the closest association with HCC. Our investigation aimed to unravel the role, underlying mechanisms, and potential therapeutic implications of CCDC137 in the context of HCC. We observed a close correlation between elevated CCDC137 expression and poor prognosis in HCC patients, along with a promotive effect on HCC progression in vitro and in vivo. Mechanistically, we identified LZTS2, a negative regulator of β-catenin, as the binding protein of CCDC137. CCDC137 facilitated K48-linked poly-ubiquitination of LZTS2 at lysine 467 via recruiting E3 ubi

SUBMITTER: Xu L 

PROVIDER: S-EPMC11742649 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature