
FXR suppresses colorectal cancer by inhibiting the Wnt/β-catenin pathway via activation of TLE3
Colorectal cancer (CRC) is the third most common and lethal cancer worldwide. Farnesoid X receptor (FXR) is a regulator of bile acid (BA) homeostasis and its expression is inversely correlated with the incidence of CRC. Moreover, our recent study discovered that dietary factors and dysregulated Wnt signaling independently alter BA profiles, some of which antagonize intestinal FXR, such as Tauro-bmuricholic acid (T-β MCA) and deoxycholic acid (DCA). These antagonistic BAs drove malignant transformations in Lgr5-expressing (Lgr5+) intestinal stem cells (ISCs), which promoted an adenoma-to-adenocarcinoma progression. Conversely, FXR agonists restored BAs homeostasis and curtailed CRC progression. However, the precise mechanism of FXR inhibiting Wnt signaling remains unclear, prompting us to investigate FXR's targets in Wnt pathway, especially in ISCs.