Galactoside 2-alpha-L-fucosyltransferase 2 (FUT2) as a novel stemness driver and therapeutic target in hepatocellular carcinoma driven by PTEN suppression (EACR 2023)
As a prove of concept, AAV8-mediated liver-directed therapy of FUT2 suppression was introduced into mice with Pten-KO HCC as a therapeutic approach.Results and DiscussionsRNA-sequencing revealed glycosphingolipid biosynthesis to be activated in mice organoids derived from Pten-KO/c-Myc HCC, compared to control organoids...Meanwhile, shRNA-mediated suppression of Fut2 was able to prolong survival of mice in HCC driven by Pten-KO.ConclusionBy introducing clean driver mutation into mice and coupling that with organoid system, we were able to identify and study, in detail, the molecular features specific to HCC driven by PTEN suppression. As an essential player in glycoprotein fucosylation, FUT2 may shed light on unique post-translational modification promoting HCC, which can be exploited for novel therapy.