| First Author | Tian M | Year | 2020 |
| Journal | Nat Commun | Volume | 11 |
| Issue | 1 | Pages | 5762 |
| PubMed ID | 33188184 | Mgi Jnum | J:297899 |
| Mgi Id | MGI:6479385 | Doi | 10.1038/s41467-020-19627-7 |
| Citation | Tian M, et al. (2020) IRF3 prevents colorectal tumorigenesis via inhibiting the nuclear translocation of beta-catenin. Nat Commun 11(1):5762 |
| abstractText | Occurrence of Colorectal cancer (CRC) is relevant with gut microbiota. However, role of IRF3, a key signaling mediator in innate immune sensing, has been barely investigated in CRC. Here, we unexpectedly found that the IRF3 deficient mice are hyper-susceptible to the development of intestinal tumor in AOM/DSS and Apc(min/+) models. Genetic ablation of IRF3 profoundly promotes the proliferation of intestinal epithelial cells via aberrantly activating Wnt signaling. Mechanically, IRF3 in resting state robustly associates with the active beta-catenin in the cytoplasm, thus preventing its nuclear translocation and cell proliferation, which can be relieved upon microbe-induced activation of IRF3. In accordance, the survival of CRC is clinically correlated with the expression level of IRF3. Therefore, our study identifies IRF3 as a negative regulator of the Wnt/beta-catenin pathway and a potential prognosis marker for Wnt-related tumorigenesis, and describes an intriguing link between gut microbiota and CRC via the IRF3-beta-catenin axis. |
