Isoliquiritigenin inhibits colorectal cancer progression by targeting the FGFR4/FASN mediated lipid metabolism pathway.

Colorectal cancer (CRC) is one of the most common malignant tumors. Isoliquiritigenin (ISL), a natural chalcone compound extracted from the roots of licorice and other plants, has demonstrated significant anti-tumor activity in various cancers. However, its specific mechanisms of action against CRC remain unclear. In this study, we investigated the molecular mechanisms underlying the effects of ISL targeting Fibroblast Growth Factor Receptor 4 (FGFR4) in CRC. Our findings revealed that FGFR4 is highly expressed in CRC cell lines, and functional assays demonstrated that silencing FGFR4 significantly inhibits cellular proliferation and migration. Further mechanistic studies showed that FGFR4 regulates fatty acid biosynthesis and the PI3K/Akt signaling pathway, as evidenced by the downregulation of Fatty Acid Synthase (FASN) and PI3K/Akt pathway proteins upon FGFR4 knockdown. Moreover, ISL significantly suppresses CRC cell proliferation and migration while disrupting tumor cell fatty acid metabolism. This study suggests that ISL may inhibit CRC progression by downregulating FGFR4 and suppressing PI3K/Akt-mediated fatty acid metabolism reprogramming.