Integrin alpha-V beta-3 (ITGAV:ITGB3) and Integrin alpha-6 beta-4 (ITGA6:ITGB4) (ITGAV:ITGB3 and ITGA6:ITGB4)

Integrins ITGAV:ITGB3 (alpha-V beta-3) and ITGA6:ITGB4 (alpha-6 beta-4) are heterodimeric transmembrane receptors that mediate critical interactions between cells and the extracellular matrix. ITGAV:ITGB3, often referred to as the vitronectin receptor, is a key regulator of angiogenesis and is frequently overexpressed in the tumor vasculature and various solid tumors, such as glioblastoma and melanoma [1, 4]. It facilitates cell migration and survival by binding to RGD-containing proteins like vitronectin and fibronectin [1, 11]. In contrast, ITGA6:ITGB4 serves as a primary receptor for laminins and is essential for the formation of hemidesmosomes in epithelial tissues [12, 16]. In a malignant context, ITGA6:ITGB4 is upregulated and promotes tumor invasion, the maintenance of cancer stem cells, and the epithelial-to-mesenchymal transition (EMT) [24, 25]. Both integrins participate in complex crosstalk with growth factor receptors, such as VEGFR and EGFR, to amplify oncogenic signaling pathways like PI3K/Akt and MAPK/ERK [3, 5, 14]. Therapeutic efforts have focused on developing monoclonal antibodies and cyclic peptides to block these receptors, although clinical success has been hampered by the lack of robust predictive biomarkers and potential paradoxical effects at sub-therapeutic doses [6, 7].

Other names

Vitronectin receptorLaminin receptorCD51/CD61CD49f/CD104Integrin alpha-V beta-3Integrin alpha-6 beta-4

Antagonism of ligand binding (such as vitronectin or laminin) to inhibit outside-in signaling pathways, thereby disrupting cell adhesion, migration, and survival while inducing apoptosis in target cells [1, 9, 12].