von Willebrand factor–integrin αvβ3 signaling pathway (VWF–αvβ3–FAK/Src)

The von Willebrand factor–integrin αvβ3 → FAK/Src signaling pathway is a multi-component biological axis that regulates vascular integrity, angiogenesis, and platelet function [Starke et al., 2011]. von Willebrand factor (VWF) serves as a ligand that binds to the integrin αvβ3 receptor on endothelial cells and platelets, particularly under conditions of vascular stress [Lenting et al., 2015]. This binding event triggers the activation of Focal Adhesion Kinase (FAK) and Src family kinases, which are essential for cytoskeletal remodeling and cell motility [Mitra et al., 2005]. In the context of cancer, this pathway is frequently exploited to facilitate tumor-associated angiogenesis and the survival of circulating tumor cells [Desgrosellier & Cheresh, 2010]. Furthermore, the pathway plays a significant role in the stabilization of arterial thrombi and the inflammatory response of the endothelium [Ruggeri, 2002]. Therapeutic targeting of this axis involves the use of integrin antagonists, such as cilengitide, or small-molecule inhibitors of the downstream kinases FAK and Src [Sulzmaier et al., 2014]. However, pharmacological intervention must balance the inhibition of pathological processes with the maintenance of normal hemostasis and vascular repair [Ley et al., 2007].

Other names

VWF-αvβ3-FAK-Src axisvon Willebrand factor-mediated integrin signalingVWF-integrin alpha-V beta-3 pathwayVWF-αvβ3-FAK/Src endothelial pathway

Inhibition of ligand binding to the integrin αvβ3 receptor or the enzymatic activity of downstream kinases FAK and Src to disrupt cellular signaling pathways involved in angiogenesis and thrombosis.