title: EMMPRIN/CD147 is a novel coreceptor of VEGFR-2 mediating its activation by VEGF.
abstract: 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.
authors.affiliation: INSERM UMR-S 976, Hôpital Saint-Louis, Paris, France.|Université Paris-Diderot, Sorbonne Paris Cité, Paris, France.|Assistance Publique-Hôpitaux de Paris, Laboratoire de Pharmacologie-Génétique, Hôpital Saint-Louis, Paris, France.
authors.forename: Farah
authors.initials: F
authors.lastname: Khayati
authors.affiliation: Joint BSC-IRB Research Program in Computational Biology, Life Sciences Department, Barcelona Supercomputing Center, Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Pérez-Cano
authors.affiliation: Département de Neurosciences, Institut Pasteur, Unité de Neurobiologie Intégrative des Systèmes Cholinergiques, Paris, France.
authors.forename: Kamel
authors.initials: K
authors.lastname: Maouche
authors.affiliation: INSERM UMR-S 976, Hôpital Saint-Louis, Paris, France.|Assistance Publique-Hôpitaux de Paris, Laboratoire de Pharmacologie-Génétique, Hôpital Saint-Louis, Paris, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Sadoux
authors.affiliation: INSERM UMR-S 976, Hôpital Saint-Louis, Paris, France.|Assistance Publique-Hôpitaux de Paris, Laboratoire de Pharmacologie-Génétique, Hôpital Saint-Louis, Paris, France.
authors.forename: Zineb
authors.initials: Z
authors.lastname: Boutalbi
authors.affiliation: INSERM UMR-S 976, Hôpital Saint-Louis, Paris, France.|Assistance Publique-Hôpitaux de Paris, Laboratoire de Pharmacologie-Génétique, Hôpital Saint-Louis, Paris, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Podgorniak
authors.affiliation: Département de Neurosciences, Institut Pasteur, Unité de Neurobiologie Intégrative des Systèmes Cholinergiques, Paris, France.
authors.forename: Uwe
authors.initials: U
authors.lastname: Maskos
authors.affiliation: Université Paris-Diderot, Sorbonne Paris Cité, Paris, France.|Plateforme d'Imagerie, IUH, Hôpital Saint-Louis, Paris, France.
authors.forename: Niclas
authors.initials: N
authors.lastname: Setterblad
authors.affiliation: Université Paris-Diderot, Sorbonne Paris Cité, Paris, France.|INSERM U728, Laboratoire de Pathologie, Hôpital Saint-Louis, AP-HP, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Janin
authors.affiliation: INSERM UMR-S 976, Hôpital Saint-Louis, Paris, France.|Université Paris-Diderot, Sorbonne Paris Cité, Paris, France.|Assistance Publique-Hôpitaux de Paris, Laboratoire de Pharmacologie-Génétique, Hôpital Saint-Louis, Paris, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Calvo
authors.affiliation: Université Paris-Diderot, Sorbonne Paris Cité, Paris, France.|Département de Dermatologie Hôpital Saint Louis, Paris, France.
authors.forename: Céleste
authors.initials: C
authors.lastname: Lebbé
authors.affiliation: CNRS-UMR 7149, Laboratoire CRRET, Créteil, France.|Université Paris 12, Créteil, France.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Menashi
authors.affiliation: Joint BSC-IRB Research Program in Computational Biology, Life Sciences Department, Barcelona Supercomputing Center, Barcelona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Fernandez-Recio
authors.affiliation: INSERM UMR-S 976, Hôpital Saint-Louis, Paris, France.|Université Paris-Diderot, Sorbonne Paris Cité, Paris, France.|Assistance Publique-Hôpitaux de Paris, Laboratoire de Pharmacologie-Génétique, Hôpital Saint-Louis, Paris, France.
authors.forename: Samia
authors.initials: S
authors.lastname: Mourah
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry; D000818:Animals; D051926:Basigin / Q000378:metabolism*; D001665:Binding Sites; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D002474:Cell-Free System; D003198:Computer Simulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008024:Ligands; D051379:Mice; D008819:Mice, Nude; D055806:Microvessels / Q000166:cytology; D016296:Mutagenesis; D016297:Mutagenesis, Site-Directed; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; C497886:BSG protein, human; D008024:Ligands; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051926:Basigin; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: EMMPRIN/CD147; VEGFR-2; coreceptor; interaction/activation
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