Integrin alpha-6 beta-4 receptor (ITGA6B4) (ITGA6B4)

Integrin alpha-6 beta-4 receptor (α6β4) is a heterodimeric transmembrane receptor that plays a critical role in maintaining the structural integrity of epithelial tissues by anchoring cells to the basement membrane through hemidesmosomes [UniProt: P17301, P23229]. Unlike most integrins that interact with the actin cytoskeleton, α6β4 uniquely links to the intermediate filament system via its large cytoplasmic domain and the adapter protein plectin [PMID: 18633355]. Its primary extracellular ligand is Laminin-332 (formerly Laminin-5), and it also interacts with other hemidesmosomal components such as BP180 (Collagen XVII) and CD151 to stabilize the adhesion complex [PMID: 23503461]. In many carcinomas, α6β4 is overexpressed and undergoes a functional shift, moving away from hemidesmosomes to associate with the actin cytoskeleton, where it cooperates with growth factor receptors like EGFR and Met to drive tumor cell migration, invasion, and survival [PMID: 18633355]. Mutations in the genes encoding the α6 or β4 subunits (ITGA6 and ITGB4) are linked to junctional epidermolysis bullosa with pyloric atresia, highlighting its essential role in tissue adhesion [NIAMS]. Therapeutic targeting of α6β4, such as with the monoclonal antibody OS2966, aims to disrupt these pro-tumorigenic signaling pathways and inhibit metastasis [OncoSynergy]. Clinical development of such therapies must carefully monitor for adverse effects like skin blistering, given the receptor's fundamental role in epithelial stability [PMID: 23503461].

Other names

CD49f/CD104alpha6beta4 integrinITGA6-ITGB4 complexLaminin receptorHemidesmosome-associated integrin

Monoclonal antibody-mediated inhibition of ligand binding and downstream signaling