A mechanism for modulation of cellular responses to VEGF: activation of the integrins.
Many similarities exist in the cellular responses elicited by VEGF and governed by integrins. Here, we identify a basis for these interrelationships: VEGF activates integrins. VEGF enhanced cell adhesion, migration, soluble ligand binding, and adenovirus gene transfer mediated by alphavbeta3 and also activated other integrins, alphavbeta5, alpha5beta1, and alpha2beta1, involved in angiogenesis. Certain tumor cells exhibited high spontaneous adhesion and migration, which were attributable to a VEGF-dependent autocrine/paracrine activation of integrins. This activation was mediated by the VEGFR2 receptor and regulated via phosphatidylinositol-3-kinase, Akt, and the PTEN signaling axis. Thus, integrin activation provides a mechanism for VEGF to induce a broad spectrum of cellular responses.
Byzova
T V
TV
Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, Cleveland Clinic Foundation, Ohio 44195, USA. byzovat@ccf.org
Goldman
C K
CK
Pampori
N
N
Thomas
K A
KA
Bett
A
A
Shattil
S J
SJ
Plow
E F
EF
D000256:Adenoviridae; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D016228:Endothelial Growth Factors / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000502:physiology*; D008222:Lymphokines / Q000494:pharmacology*; D008545:Melanoma; D018919:Neovascularization, Physiologic; D020033:Protein Isoforms / Q000494:pharmacology; D038981:Receptors, Collagen; D017469:Receptors, Fibronectin / Q000502:physiology; D019030:Receptors, Vitronectin / Q000502:physiology; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D019096:Vitronectin / Q000502:physiology
D016228:Endothelial Growth Factors; D016023:Integrins; D008222:Lymphokines; D020033:Protein Isoforms; D038981:Receptors, Collagen; D017469:Receptors, Fibronectin; D019030:Receptors, Vitronectin; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D019096:Vitronectin; C064660:integrin alphaVbeta5