biostudies-literatureBatlle REuropean Research CouncilFundació la Marató de TV3 (TV3 Marathon Foundation)Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness)Departament d'Innovació, Universitats i Empresa, Generalitat de Catalunya (Department of Innovation, Education and Enterprise, Government of Catalonia)3071https://www.ebi.ac.uk/biostudies/studies/S-EPMC6624205biostudies-literatureUnknown10(1)The formation of new blood vessels is essential for normal development, tissue repair and tumor growth. Here we show that inhibition of the kinase p38α enhances angiogenesis in human and mouse colon tumors. Mesenchymal cells can contribute to tumor angiogenesis by regulating proliferation and migration of endothelial cells. We show that p38α negatively regulates an angiogenic program in mesenchymal stem/stromal cells (MSCs), multipotent progenitors found in perivascular locations. This program includes the acquisition of an endothelial phenotype by MSCs mediated by both TGF-β and JNK, and negatively regulated by p38α. Abrogation of p38α in mesenchymal cells increases tumorigenesis, which correlates with enhanced angiogenesis. Using genetic models, we show that p38α regulates the acquisition of an endothelial-like phenotype by mesenchymal cells in colon tumors and damage tissue. Taken together, our results indicate that p38α in mesenchymal cells restrains a TGF-β-induced angiogenesis program including their ability to transdifferentiate into endothelial cells.Nature communicationsRegulation of tumor angiogenesis and mesenchymal-endothelial transition by p38α through TGF-β and JNK signaling.PMC662420529466520133430ERC 294665SAF2016-81043-R2017 SGR-557Batlle RGutierrez-Prat NIgea ANebreda ARLlonch EAndres EGonzalez LBerenguer-Llergo AfalseRegulation of tumor angiogenesis and mesenchymal-endothelial transition by p38α through TGF-β and JNK signaling.The formation of new blood vessels is essential for normal development, tissue repair and tumor growth. Here we show that inhibition of the kinase p38α enhances angiogenesis in human and mouse colon tumors. Mesenchymal cells can contribute to tumor angiogenesis by regulating proliferation and migration of endothelial cells. We show that p38α negatively regulates an angiogenic program in mesenchymal stem/stromal cells (MSCs), multipotent progenitors found in perivascular locations. This program includes the acquisition of an endothelial phenotype by MSCs mediated by both TGF-β and JNK, and negatively regulated by p38α. Abrogation of p38α in mesenchymal cells increases tumorigenesis, which correlates with enhanced angiogenesis. Using genetic models, we show that p38α regulates the acquisition of an endothelial-like phenotype by mesenchymal cells in colon tumors and damage tissue. Taken together, our results indicate that p38α in mesenchymal cells restrains a TGF-β-induced angiogenesis program including their ability to transdifferentiate into endothelial cells.2019-01-01T00:00:00Z2019 Jul2026-05-02T19:38:43.541Z2019-07-25T07:09:08ZS-EPMC66242053129685610.1038/s41467-019-10946-y