| First Author | Yuan Q | Year | 2021 |
| Journal | Cell Rep | Volume | 34 |
| Issue | 5 | Pages | 108724 |
| PubMed ID | 33535045 | Mgi Jnum | J:304311 |
| Mgi Id | MGI:6694779 | Doi | 10.1016/j.celrep.2021.108724 |
| Citation | Yuan Q, et al. (2021) MyD88 in myofibroblasts enhances colitis-associated tumorigenesis via promoting macrophage M2 polarization. Cell Rep 34(5):108724 |
| abstractText | 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 alphavbeta3 and CD44, leading to activation of the STAT3/PPARgamma 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. |
