Integrin alpha-V subunit (ITGAV) (ITGAV)

Integrins containing the alpha-V subunit (ITGAV/CD51) are a subgroup of heterodimeric transmembrane receptors that play a pivotal role in cell-extracellular matrix (ECM) interactions (UniProt P06756). The alpha-V subunit can pair with five different beta subunits (beta-1, beta-3, beta-5, beta-6, and beta-8) to form functional receptors that primarily recognize the Arg-Gly-Asp (RGD) tripeptide motif in ligands such as vitronectin, fibronectin, and fibrinogen (Ley et al., 2016, Nature Reviews Endocrinology). These receptors are essential for processes like angiogenesis, cell migration, and the mechanical activation of latent TGF-beta, a master regulator of fibrosis (Henderson et al., 2013, Nature Medicine). In pathological states, alpha-V integrins are frequently upregulated, contributing to tumor progression, metastasis, and the development of fibrotic diseases in the lungs, liver, and kidneys (PubMed: 23995282). Therapeutic strategies targeting these integrins include monoclonal antibodies like Abituzumab and small molecule inhibitors like PLN-74809 designed to block ligand binding or TGF-beta activation (ClinicalTrials.gov). While early clinical trials in oncology faced challenges, alpha-V integrins remain high-interest targets for treating chronic fibrotic conditions and specific solid tumors (StatPearls: Integrins).

Other names

CD51Vitronectin receptor subunit alphaMSK21Integrin alpha VAntigen identified by monoclonal antibody L230

Drugs targeting alpha-V integrins typically act as competitive antagonists that block the binding of the RGD (Arg-Gly-Asp) motif found in extracellular matrix proteins (Ley et al., 2016, Nature Reviews Endocrinology). Specifically, inhibitors of alpha-V-beta-6 and alpha-V-beta-8 prevent the physical pulling and release of active TGF-beta from its latent complex, thereby halting pro-fibrotic signaling pathways (Henderson et al., 2013, Nature Medicine). Monoclonal antibodies may also induce receptor internalization or block downstream signaling cascades like the FAK/Src pathway (PubMed: 24631835).