Oncotarget

Research Papers:

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

Farah Khayati _, Laura Pérez-Cano, Kamel Maouche, Aurélie Sadoux, Zineb Boutalbi, Marie-Pierre Podgorniak, Uwe Maskos, Niclas Setterblad, Anne Janin, Fabien Calvo, Céleste Lebbé, Suzanne Menashi, Juan Fernandez-Recio, Samia Mourah

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Abstract

Farah Khayati1,2,3, Laura Pérez-Cano4, Kamel Maouche5, Aurélie Sadoux1,3, Zineb Boutalbi1,3, Marie-Pierre Podgorniak1,3, Uwe Maskos5, Niclas Setterblad2,6, Anne Janin2,7, Fabien Calvo1,2,3, Céleste Lebbé2,8, Suzanne Menashi9,10, Juan Fernandez-Recio4, Samia Mourah1,2,3

1INSERM UMR-S 976, Hôpital Saint-Louis, Paris, France

2Université Paris-Diderot, Sorbonne Paris Cité, Paris, France

3Assistance Publique-Hôpitaux de Paris, Laboratoire de Pharmacologie-Génétique, Hôpital Saint-Louis, Paris, France

4Joint BSC-IRB Research Program in Computational Biology, Life Sciences Department, Barcelona Supercomputing Center, Barcelona, Spain

5Département de Neurosciences, Institut Pasteur, Unité de Neurobiologie Intégrative des Systèmes Cholinergiques, Paris, France

6Plateforme d'Imagerie, IUH, Hôpital Saint-Louis, Paris, France

7INSERM U728, Laboratoire de Pathologie, Hôpital Saint-Louis, AP-HP, Paris, France

8Département de Dermatologie Hôpital Saint Louis, Paris, France

9CNRS-UMR 7149, Laboratoire CRRET, Créteil, France

10Université Paris 12, Créteil, France

Correspondence to:

Samia Mourah, e-mail: samia.mourah@sls.aphp.fr

Keywords: VEGFR-2, EMMPRIN/CD147, interaction/activation, coreceptor

Received: July 21, 2014     Accepted: December 07, 2014     Published: March 23, 2015

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.

Author Information

Farah Khayati
Primary Contact  _

Laura Pérez-Cano

Kamel Maouche

Aurélie Sadoux

Zineb Boutalbi

Marie-Pierre Podgorniak

Uwe Maskos

Niclas Setterblad

Anne Janin

Fabien Calvo

Céleste Lebbé

Suzanne Menashi

Juan Fernandez-Recio

Samia Mourah


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