Folliculin depletion results in liver cell damage and cholangiocarcinoma through MiT/TFE activation.

ABSTRACT: Mutations in the tumor suppressor gene Folliculin (FLCN) are responsible for Birt-Hogg-Dube' (BHD) syndrome, a rare inherited condition that predisposes affected individuals to skin tumors, pulmonary cysts, and kidney tumors. FLCN regulates key cellular pathways, including TFEB, TFE3, and mTORC1, which are critical for maintaining cell homeostasis. Loss of FLCN leads to both hyperactivation of mTORC1 and constitutive activation of TFEB and TFE3, contributing to tumorigenesis. While previous studies showed that Flcn liver-specific conditional knockout (Flcn^LiKO) mice are protected from developing liver fibrosis and damage upon high-fat diet exposure, the potential role of FLCN loss in liver carcinogenesis remained unexplored. Here, we demonstrate that hepatic loss of FLCN in mice

SUBMITTER: Custode BM 

PROVIDER: S-EPMC12325662 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature