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- Title
IRF3 prevents colorectal tumorigenesis via inhibiting the nuclear translocation of β-catenin.
- Authors
Tian, Miao; Wang, Xiumei; Sun, Jihong; Lin, Wenlong; Chen, Lumin; Liu, Shengduo; Wu, Ximei; Shi, Liyun; Xu, Pinglong; Cai, Xiujun; Wang, Xiaojian
- Abstract
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 Apcmin/+ 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 β-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/β-catenin pathway and a potential prognosis marker for Wnt-related tumorigenesis, and describes an intriguing link between gut microbiota and CRC via the IRF3-β-catenin axis. The alternative mechanisms of innate immunity in tumorigenesis of colorectal cancers are unclear. Here, the authors report a non-canonical function of IRF3, a mediator of innate immune signalling, in the suppression of colorectal tumorigenesis and this is via the inhibition of Wnt/β-catenin pathway.
- Subjects
NEOPLASTIC cell transformation; GUT microbiome; WNT signal transduction; CATENINS; INTESTINAL tumors; COLON cancer; WNT genes
- Publication
Nature Communications, 2020, Vol 11, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-020-19627-7