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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(More)
Prothrombin activation is a pivotal event in thrombosis and hemostasis because thrombin can mediate fibrin formation and can activate and aggregate platelets. Platelet aggregation depends upon the binding of adhesive proteins to integrin alphaIIbbeta3 on the platelet surface. In the present study, a novel interface between the blood coagulation system and(More)
The process of angiogenesis is crucial for progression and metastasis of the majority of solid tumors including melanomas. The current review summarizes existing knowledge of the mechanisms of angiogenesis in melanoma, as well as current anti-angiogenic therapeutic strategies and their targets. We focus primarily on the role of key growth factors that are(More)
Akt kinases control essential cellular functions, including proliferation, apoptosis, metabolism and transcription, and have been proposed as promising targets for treatment of angiogenesis-dependent pathologies, such as cancer and ischemic injury. But their precise roles in neovascularization remain elusive. Here we show that Akt1 is the predominant(More)
The process of postnatal angiogenesis plays a crucial role in pathogenesis of numerous diseases, including but not limited to tumor growth/metastasis, diabetic retinopathy, and in tissue remodeling upon injury. However, the molecular events underlying this complex process are not well understood and numerous issues remain controversial, including the(More)
The functional responses of endothelial cells are dependent on signaling from peptide growth factors and the cellular adhesion receptors, integrins. These include cell adhesion, migration, and proliferation, which, in turn, are essential for more complex processes such as formation of the endothelial tube network during angiogenesis. This study identifies(More)
The molecular mechanism leading to the cancer metastasis to bone is poorly understood but yet determines prognosis and therapy. Here, we define a new molecular pathway that may account for the extraordinarily high osteotropism of prostate cancer. By using SPARC (secreted protein, acidic and rich in cysteine)-deficient mice and recombinant SPARC, we(More)
The cross-talk between receptor tyrosine kinases and integrin receptors are known to be crucial for a number of cellular functions. On endothelial cells, an interaction between integrin alphavbeta3 and VEGFR2 seems to be particularly important process during vascularization. Importantly, the functional association between VEGFR2 and integrin alphavbeta3 is(More)
Arterial morphogenesis is an important and poorly understood process. In particular, the signaling events controlling arterial formation have not been established. We evaluated whether alterations in the balance between ERK1/2 and PI3K signaling pathways could stimulate arterial formation in the setting of defective arterial morphogenesis in mice and(More)
Kindlin-2, a widely distributed cytoskeletal protein, has been implicated in integrin activation, and its absence is embryonically lethal in mice and causes severe developmental defects in zebrafish. Knockdown of kindlin-2 levels in endothelial cells resulted in defective adhesive and migratory responses, suggesting that angiogenesis might be aberrant even(More)