2026-07-21T07:35:37Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/68192024-11-29T23:11:06Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Youssif, Catrin author Cubillos-Rojas, Monica author Comalada, Mònica author Llonch, Elisabeth author Perna, Cristian author Djouder, Nabil author Nebreda, Angel R author 2018-07 The protein kinase p38α plays a key role in cell homeostasis, and p38α signaling in intestinal epithelial cells protects against colitis-induced tumorigenesis. However, little is known on the contribution of p38α signaling in intestinal stromal cells. Here, we show that myeloid cell-specific downregulation of p38α 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 p38α 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 p38α in colon samples from patients with ulcerative colitis or colon cancer. Altogether, our results uncover an important role for myeloid IGF-1 downstream of p38α 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. EMBO Mol Med. 2018 ;10(7). pii: e8403. 10.15252/emmm.201708403 1757-4684 1757-4676 EMBO molecular medicine 29907597 http://hdl.handle.net/20.500.12105/6819 IGF‐1 Colon tumorigenesis Intestinal inflammation Macrophage p38 MAPK Myeloid p38α signaling promotes intestinal IGF-1 production and inflammation-associated tumorigenesis