Distinct molecular pathways regulated by activated AKT and YAP signaling during intrahepatic cholangiocarcinoma progression: Roles of AKT and YAP during iCCA - PubMed
a day ago
- #iCCA
- #YAP
- #AKT
- Activated AKT and YAP signaling play distinct roles in intrahepatic cholangiocarcinoma (iCCA) progression.
- Two doxycycline-inducible iCCA mouse models (Akt/TRE-YAP and TRE-Akt/YAP) were developed to study selective inhibition of YAP or AKT.
- YAP suppression initially caused tumor regression but led to steatosis-HCC due to persistent AKT signaling.
- AKT suppression induced profound iCCA regression with minimal tumor burden.
- AKT regulates tumor metabolic pathways, while YAP controls iCCA differentiation and the immune microenvironment.
- YAP inhibition depleted neutrophils and increased CD4+ and CD8+ T cell infiltration but these T cells expressed PD-1.
- Combined YAP suppression and anti-PD-L1 treatment enhanced tumor regression.
- YAP is identified as a key regulator of the tumor immune microenvironment (TIME) in iCCA.
- The findings support combining YAP inhibition with immune checkpoint inhibitors (ICIs) for iCCA treatment.