2. Academic Validation
  3. MyD88 in myofibroblasts enhances colitis-associated tumorigenesis via promoting macrophage M2 polarization

MyD88 in myofibroblasts enhances colitis-associated tumorigenesis via promoting macrophage M2 polarization

  • Cell Rep. 2021 Feb 2;34(5):108724. doi: 10.1016/j.celrep.2021.108724.
Qi Yuan 1,  Jianchun Gu 2,  Jie Zhang 1,  Shi Liu 1,  Qinchuan Wang 3,  Tian Tian 1,  Zhinan Chen 4,  Jinhua Zhang 5
Affiliations

Affiliations

  • 1 The College of Life Science and Bioengineering, Beijing Jiaotong University, Beijing, P.R. China.
  • 2 Department of Oncology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • 3 Department of Surgical Oncology, Affiliated Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China.
  • 4 The College of Life Science and Bioengineering, Beijing Jiaotong University, Beijing, P.R. China; Cell Engineering Research Center and Department of Cell Biology, State Key Laboratory of Cancer, Fourth Military Medical University, Xi'an, P.R. China.
  • 5 The College of Life Science and Bioengineering, Beijing Jiaotong University, Beijing, P.R. China. Electronic address: zhangjh@bjtu.edu.cn.
PMID: 33535045 DOI: 10.1016/j.celrep.2021.108724
Abstract

The signal adaptor MyD88, an essential component of TLR signaling, plays an important role in gut-microbiome interactions. However, its contribution to colitis-associated Cancer (CAC) is still controversial. Far less is known about the specific effects of MyD88 signaling in myofibroblasts in CAC development. Here, we used a CAC mouse model in which MyD88 was selectively depleted in myofibroblasts. Myofibroblast MyD88-deficient mice are resistant to azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced tumorigenesis, as evidenced by the decrease in the number and sizes of tumors. MyD88 deficiency in myofibroblasts attenuates intestinal epithelial cell (IEC) proliferation after acute DSS-induced colitis. Furthermore, MyD88 signaling in myofibroblasts increases the secretion of osteopontin (OPN), which promotes macrophage M2 polarization through binding to αvβ3 and CD44, leading to activation of the STAT3/PPARγ pathway. Thus, MyD88 signaling in myofibroblasts crucially contributes to colorectal Cancer development and provides a promising therapeutic target for the prevention of colitis-associated carcinogenesis.

Keywords

MyD88; colitis-associated cancer; macrophage polarization.

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