| First Author | Chiodelli P | Year | 2017 |
| Journal | Oncogene | Volume | 36 |
| Issue | 47 | Pages | 6531-6541 |
| PubMed ID | 28783175 | Mgi Jnum | J:251149 |
| Mgi Id | MGI:6101158 | Doi | 10.1038/onc.2017.243 |
| Citation | Chiodelli P, et al. (2017) Contribution of vascular endothelial growth factor receptor-2 sialylation to the process of angiogenesis. Oncogene 36(47):6531-6541 |
| abstractText | Vascular endothelial growth factor receptor-2 (VEGFR2) is the main pro-angiogenic receptor expressed by endothelial cells (ECs). Using surface plasmon resonance, immunoprecipitation, enzymatic digestion, immunofluorescence and cross-linking experiments with specific sugar-binding lectins, we demonstrated that VEGFR2 bears both alpha,1-fucose and alpha(2,6)-linked sialic acid (NeuAc). However, only the latter is required for VEGF binding to VEGFR2 and consequent VEGF-dependent VEGFR2 activation and motogenic response in ECs. Notably, downregulation of beta-galactoside alpha(2,6)-sialyltransferase expression by short hairpin RNA transduction inhibits VEGFR2 alpha(2,6) sialylation that is paralleled by an increase of beta-galactoside alpha(2,3)-sialyltransferase expression. This results in an ex-novo alpha(2,3)-NeuAc sialylation of the receptor that functionally replaces the lacking alpha(2,6)-NeuAc, thus allowing VEGF/VEGFR2 interaction. In keeping with the role of VEGFR2 sialylation in angiogenesis, the alpha(2,6)-NeuAc-binding lectin Sambucus nigra (SNA) prevents VEGF-dependent VEGFR2 autophosphorylation and EC motility, proliferation and motogenesis. In addition, SNA exerts a VEGF-antagonist activity in tridimensional angiogenesis models in vitro and in the chick-embryo chorioallantoic membrane neovascularization assay and mouse matrigel plug assay in vivo. In conclusion, VEGFR2-associated NeuAc plays an important role in modulating VEGF/VEGFR2 interaction, EC pro-angiogenic activation and neovessel formation. VEGFR2 sialylation may represent a target for the treatment of angiogenesis-dependent diseases. |
