Alpha-V integrin heterodimer (αv integrins)

Alpha-V (αv) integrins are a distinct group of heterodimeric cell surface receptors composed of the αv subunit (ITGAV/CD51) non-covalently associated with one of five beta subunits: β1, β3, β5, β6, or β8 (Ley et al., 2016, Nature Reviews Molecular Cell Biology). These receptors are characterized by their ability to recognize the Arginine-Glycine-Aspartic acid (RGD) motif in various extracellular matrix (ECM) ligands, including vitronectin, fibronectin, and fibrinogen (Nieberler et al., 2017, Cancers). Beyond structural adhesion, αv integrins are pivotal in signal transduction and the spatial activation of latent Transforming Growth Factor-beta (TGF-β), particularly the αvβ6 and αvβ8 isoforms which are essential for TGF-β1 and TGF-β3 maturation (Henderson & Sheppard, 2013, Nature). In clinical contexts, αv integrins are highly relevant as they are frequently overexpressed in many solid tumors, where they promote angiogenesis, tumor cell survival, and metastasis. They are also recognized as key drivers of tissue fibrosis in the lungs, liver, and kidneys by promoting myofibroblast activation (Conroy et al., 2016, Arteriosclerosis, Thrombosis, and Vascular Biology). Pharmacological targeting has focused on monoclonal antibodies and small-molecule RGD mimetics designed to disrupt ligand binding or TGF-β activation. While many candidates like Cilengitide showed early promise, clinical success has been tempered by the complexity of integrin signaling and the potential for paradoxical receptor activation at sub-therapeutic doses (Koivunen et al., 1999, Nature Biotechnology).

Other names

CD51Integrin alpha-VITGAVVitronectin receptorAlpha-V subunit integrins

Competitive inhibition of the RGD-binding pocket to prevent cell-extracellular matrix adhesion and signaling, and blockade of the mechanical force required to release active TGF-beta from its latent complex.