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dc.contributor.authorYoussif, Catrin
dc.contributor.authorCubillos-Rojas, Monica
dc.contributor.authorComalada, Mònica
dc.contributor.authorLlonch, Elisabeth
dc.contributor.authorPerna, Cristian
dc.contributor.authorDjouder, Nabil 
dc.contributor.authorNebreda, Angel R
dc.date.accessioned2018-12-12T09:46:55Z
dc.date.available2018-12-12T09:46:55Z
dc.date.issued2018-07
dc.identifier.citationEMBO Mol Med. 2018 ;10(7). pii: e8403.es_ES
dc.identifier.issn1757-4676es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/6819
dc.description.abstractThe 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.es_ES
dc.description.sponsorshipwe are grateful to Nadia Rosenthal and Lina Wang for providing IGF-1-DMC mice. C.Y. is very grateful to Joan Guinovart for his personal and financial support. We acknowledge the excellent technical assistance of Neus Pratsand the IRB Histology facility members, Camille Stephan-Otto Attolini andAdria Caballe from the IRB Biostatistics/Bioinformatics facility, and JaumeComas and the UB fluorescence-activated cell sorting facility. We thankTeresa Rodrigo Calduch, head of the Unitat d’Experimentació Animal deFarmàcia de la Universitat de Barcelona. We are grateful to the Nebredagroup at IRB Barcelona for their support and many useful discussions. Thiswork was supported by grants from the European Commission (AdvancedERC294665), Fundación Marató TV3(20133430), Spanish MINECO (SAF2016-81043-R), and AGAUR (2014SRG-535 and 2017SGR-557). C.Y. acknowledges a“La Caixa”predoctoral fellowship. IRB Barcelona is the recipient of institu-tional funding from MINECO (Government of Spain) through the Centres of Excellence Severo Ochoa award and from the CERCA Program of the Catalan Government.es_ES
dc.language.isoenges_ES
dc.publisherWileyes_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectIGF‐1es_ES
dc.subjectcolon tumorigenesises_ES
dc.subjectintestinal inflammationes_ES
dc.subjectmacrophagees_ES
dc.subjectp38 MAPKes_ES
dc.titleMyeloid p38α signaling promotes intestinal IGF-1 production and inflammation-associated tumorigenesises_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID29907597es_ES
dc.format.volume10es_ES
dc.format.number7es_ES
dc.format.pagee8403es_ES
dc.identifier.doi10.15252/emmm.201708403es_ES
dc.contributor.funderEuropean Research Council
dc.contributor.funderFundación La Caixa
dc.contributor.funderMinisterio de Ciencia e Innovación (España)
dc.contributor.funderFundación La Mataró TV3
dc.description.peerreviewedes_ES
dc.identifier.e-issn1757-4684es_ES
dc.relation.publisherversionhttps://doi.org/10.15252/emmm.201708403.es_ES
dc.identifier.journalEMBO molecular medicinees_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Factores de Crecimiento, Nutrientes y Cánceres_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/294665es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2016-81043-Res_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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