| First Author | Fu T | Year | 2019 |
| Journal | Cell | Volume | 176 |
| Issue | 5 | Pages | 1098-1112.e18 |
| PubMed ID | 30794774 | Mgi Jnum | J:286176 |
| Mgi Id | MGI:6390093 | Doi | 10.1016/j.cell.2019.01.036 |
| Citation | Fu T, et al. (2019) FXR Regulates Intestinal Cancer Stem Cell Proliferation. Cell 176(5):1098-1112.e18 |
| abstractText | Increased levels of intestinal bile acids (BAs) are a risk factor for colorectal cancer (CRC). Here, we show that the convergence of dietary factors (high-fat diet) and dysregulated WNT signaling (APC mutation) alters BA profiles to drive malignant transformations in Lgr5-expressing (Lgr5(+)) cancer stem cells and promote an adenoma-to-adenocarcinoma progression. Mechanistically, we show that BAs that antagonize intestinal farnesoid X receptor (FXR) function, including tauro-beta-muricholic acid (T-betaMCA) and deoxycholic acid (DCA), induce proliferation and DNA damage in Lgr5(+) cells. Conversely, selective activation of intestinal FXR can restrict abnormal Lgr5(+) cell growth and curtail CRC progression. This unexpected role for FXR in coordinating intestinal self-renewal with BA levels implicates FXR as a potential therapeutic target for CRC. |
