EMMPRIN/CD147 is a novel coreceptor of VEGFR-2 mediating its activation by VEGF

EMMPRIN/CD147 is mainly known for its protease inducing function but a role in promoting tumor angiogenesis has also been demonstrated. This study provides evidence that EMMPRIN is a new coreceptor for the VEGFR-2 tyrosine kinase receptor in both endothelial and tumor cells, as it directly interacts...

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Detalles Bibliográficos
Autores: Khayati, Farah, Pérez-Cano, Laura, Maouche, Kamel, Sadoux, Aurélie, Boutalbi, Zineb, Podgorniak, Marie-Pierre, Maskos, Uwe, Setterblad, Niclas, Janin, Anne, Calvo, Fabien, Lebbé, Céleste, Menashi, Suzanne, Fernández-Recio, Juan, Mourah, Samia
Tipo de recurso: artículo
Fecha de publicación:2015
País:España
Institución:Universitat Politècnica de Catalunya (UPC)
Repositorio:UPCommons. Portal del coneixement obert de la UPC
Idioma:inglés
OAI Identifier:oai:upcommons.upc.edu:2117/84621
Acceso en línea:https://hdl.handle.net/2117/84621
https://dx.doi.org/10.18632/oncotarget.2870
Access Level:acceso abierto
Palabra clave:Tumor proteins
VEGFR-2
EMMPRIN/CD147
Interaction/activation
Coreceptor
Marcadors tumorals
Àrees temàtiques de la UPC::Enginyeria biomèdica
Descripción
Sumario:EMMPRIN/CD147 is mainly known for its protease inducing function but a role in promoting tumor angiogenesis has also been demonstrated. This study provides evidence that EMMPRIN is a new coreceptor for the VEGFR-2 tyrosine kinase receptor in both endothelial and tumor cells, as it directly interacts with it and regulates its activation by its VEGF ligand, signalling and functional consequences both in vitro and in vivo. Computational docking analyses and mutagenesis studies identified a molecular binding site in the extracellular domain of EMMPRIN located close to the cell membrane and containing the amino acids 195/199. EMMPRIN is overexpressed in cancer and hence is able to further potentiate VEGFR-2 activation, suggesting that a combinatory therapy of an antiangiogenic drug together with an inhibitor of EMMPRIN/VEGFR-2 interaction may have a greater impact on inhibiting angiogenesis and malignancy.