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IRF3 prevents colorectal tumorigenesis via inhibiting the nuclear translocation of β-catenin

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Listed:
  • Miao Tian

    (Zhejiang University)

  • Xiumei Wang

    (Zhejiang University)

  • Jihong Sun

    (Zhejiang University)

  • Wenlong Lin

    (Zhejiang University)

  • Lumin Chen

    (Zhejiang University)

  • Shengduo Liu

    (Zhejiang University)

  • Ximei Wu

    (Zhejiang University)

  • Liyun Shi

    (Nanjing University of Chinese Medicine)

  • Pinglong Xu

    (Zhejiang University)

  • Xiujun Cai

    (Zhejiang University School of Medicine)

  • Xiaojian Wang

    (Zhejiang University)

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.

Suggested Citation

  • Miao Tian & Xiumei Wang & Jihong Sun & Wenlong Lin & Lumin Chen & Shengduo Liu & Ximei Wu & Liyun Shi & Pinglong Xu & Xiujun Cai & Xiaojian Wang, 2020. "IRF3 prevents colorectal tumorigenesis via inhibiting the nuclear translocation of β-catenin," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19627-7
    DOI: 10.1038/s41467-020-19627-7
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