Journal
ONCOTARGET
Volume 6, Issue 12, Pages 9766-9780Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.2870
Keywords
VEGFR-2; EMMPRIN/CD147; interaction/activation; coreceptor
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Funding
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- La Ligue Nationale contre le Cancer (LNCC)
- La Societe Francaise de Dermatologie
- Universite Paris Diderot
- Canceropole-Ile de France
- Fondation ARC pour la Recherche sur le Cancer
- Spanish Ministry of Science
- Plan NacionalI+D+iMICINN [BIO2010-22324]
- Association Saint-Louis
- Ministere de la Recherche
- Conseil Regional d'Ile-de-France
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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.
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