| First Author | Youssif C | Year | 2018 |
| Journal | EMBO Mol Med | Volume | 10 |
| Issue | 7 | PubMed ID | 29907597 |
| Mgi Jnum | J:310361 | Mgi Id | MGI:6762681 |
| Doi | 10.15252/emmm.201708403 | Citation | Youssif C, et al. (2018) Myeloid p38alpha signaling promotes intestinal IGF-1 production and inflammation-associated tumorigenesis. EMBO Mol Med 10(7) |
| abstractText | The protein kinase p38alpha plays a key role in cell homeostasis, and p38alpha signaling in intestinal epithelial cells protects against colitis-induced tumorigenesis. However, little is known on the contribution of p38alpha signaling in intestinal stromal cells. Here, we show that myeloid cell-specific downregulation of p38alpha protects mice against inflammation-associated colon tumorigenesis. The reduced tumorigenesis correlates with impaired detection in the colon of crucial chemokines for immune cell recruitment. We identify insulin-like growth factor-1 (IGF-1) as a novel mediator of the p38alpha pathway in macrophages. Moreover, using genetic and pharmacological approaches, we confirm the implication of IGF-1 produced by myeloid cells in colon inflammation and tumorigenesis. We also show a correlation between IGF-1 pathway activation and the infiltration of myeloid cells with active p38alpha in colon samples from patients with ulcerative colitis or colon cancer. Altogether, our results uncover an important role for myeloid IGF-1 downstream of p38alpha in colitis-associated tumorigenesis and suggest the interest in evaluating IGF-1 therapies for inflammation-associated intestinal diseases, taking into consideration IGF-1 signaling and immune cell infiltration in patient biopsies. |
