2026-07-21T07:35:38Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/68192024-11-29T23:11:06Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Youssif, Catrin
author
Cubillos-Rojas, Monica
author
Comalada, Mònica
author
Llonch, Elisabeth
author
Perna, Cristian
author
Djouder, Nabil
author
Nebreda, Angel R
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Fundación La Caixa
funder
Ministerio de Ciencia e Innovación (España)
funder
Fundación La Marató TV3
2018-12-12T09:46:55Z
2018-12-12T09:46:55Z
2018-07
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
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.
eng
IGF‐1
Colon tumorigenesis
Intestinal inflammation
Macrophage
p38 MAPK
Myeloid p38α signaling promotes intestinal IGF-1 production and inflammation-associated tumorigenesis
journal article
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Myeloidp38Ssignaling_2018.pdf
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Myeloidp38Ssignaling_2018.pdf.txt