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Disrupting YAP phase separation attenuates the development of primary liver cancer in animal models

ABSTRACT: In these murine liver cancer samples, we used specific antibody detection to find endogenous YAP formation condensates in the focal area, a phenomenon also observed in human liver cancer tissues. Deletion, mutagenesis and replacement assays of the coiled-coil (CC) domain demonstrate a critical role of activated YAP condensation in c-Myc-induced hepatoma, myr-AKT-induced intrahepatic cholangiocarcinoma, and N90-CTNNB1-induced hepatoblastoma. Transcriptome sequencing revealed that YAP phase separation inhibits AMPK activation and promotes c-Myc-induced hepatoma development. Our research indicates that condensates driven by YAP phase separation enrich TAK1, an AMPK-activated upstream kinase, potentially creating a physical barrier to AMPK phosphorylation activation. In addition, we further demonstrated that a specific peptide derived from TEAD1 disrupts the formation of YAP condensates and attenuates the development of these primary liver cancers.

ORGANISM(S): Mus musculus

PROVIDER: GSE277433 | GEO | 2025/09/18

REPOSITORIES: GEO

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