Distinct phenotypic consequences of cholangiocarcinoma-associated FGFR2 alterations depend on biliary epithelial maturity.

ABSTRACT: Epithelial cancers disrupt tissue architecture and are often driven by mutations in genes that normally play important roles in epithelial morphogenesis. The intrahepatic biliary system is an epithelial tubular network that forms within the developing liver via the de novo initiation and expansion of apical lumens. Intrahepatic biliary tumors are often driven by different types of mutations in the FGFR2 receptor tyrosine kinase which plays important roles in epithelial morphogenesis in other developmental settings. Using a physiologic and quantitative 3D model we have found that FGFR signaling is important for biliary morphogenesis and that oncogenic FGFR2 mutants disrupt biliary architecture. Importantly, we found that both the trafficking and signaling of normal FGFR2 and the phen

SUBMITTER: O'Loughlin E 

PROVIDER: S-EPMC11398422 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature