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

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

  • Oncotarget. 2015;6(12):9766-80. doi: 10.18632/oncotarget.2870.
Farah Khayati 1 2 3,  Laura Pérez-Cano 4,  Kamel Maouche 5,  Aurélie Sadoux 1 3,  Zineb Boutalbi 1 3,  Marie-Pierre Podgorniak 1 3,  Uwe Maskos 5,  Niclas Setterblad 2 6,  Anne Janin 2 7,  Fabien Calvo 1 2 3,  Céleste Lebbé 2 8,  Suzanne Menashi 9 10,  Juan Fernandez-Recio 4,  Samia Mourah 1 2 3
Affiliations

Affiliations

  • 1 INSERM UMR-S 976, Hôpital Saint-Louis, Paris, France.
  • 2 Université Paris-Diderot, Sorbonne Paris Cité, Paris, France.
  • 3 Assistance Publique-Hôpitaux de Paris, Laboratoire de Pharmacologie-Génétique, Hôpital Saint-Louis, Paris, France.
  • 4 Joint BSC-IRB Research Program in Computational Biology, Life Sciences Department, Barcelona Supercomputing Center, Barcelona, Spain.
  • 5 Département de Neurosciences, Institut Pasteur, Unité de Neurobiologie Intégrative des Systèmes Cholinergiques, Paris, France.
  • 6 Plateforme d'Imagerie, IUH, Hôpital Saint-Louis, Paris, France.
  • 7 INSERM U728, Laboratoire de Pathologie, Hôpital Saint-Louis, AP-HP, Paris, France.
  • 8 Département de Dermatologie Hôpital Saint Louis, Paris, France.
  • 9 CNRS-UMR 7149, Laboratoire CRRET, Créteil, France.
  • 10 Université Paris 12, Créteil, France.
PMID: 25825981 DOI: 10.18632/oncotarget.2870
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.

Keywords

EMMPRIN/CD147; VEGFR-2; coreceptor; interaction/activation.

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