Integrin alpha-V beta-6 (αvβ6) (ITGAV:ITGB6 or αvβ6)

Integrin alpha-V beta-6 (αvβ6) is a heterodimeric cell surface receptor composed of non-covalently linked αv and β6 subunits that is expressed exclusively on epithelial cells.[3][4] The β6 subunit pairs uniquely and specifically with only the αv subunit, distinguishing it from other integrin β subunits that associate with multiple α partners.[3] The primary function of αvβ6 is to activate transforming growth factor-β1 (TGF-β1) by binding to the latency-associated peptide (LAP) in the extracellular matrix and applying mechanical force to release the active cytokine.[3][4][5] This activation regulates critical biological processes including cell proliferation, differentiation, angiogenesis, epithelial-mesenchymal transition, and immune suppression.[3] αvβ6 serves as a validated therapeutic target in cancer, particularly in epithelial malignancies such as pancreatic ductal adenocarcinoma and cholangiocarcinoma, where it is frequently overexpressed and promotes tumor progression through multiple mechanisms.[2][3] The integrin supports cancer cell migration and invasion by promoting matrix metalloproteinase secretion, activating MAP kinase and Akt signaling pathways, and facilitating epithelial-mesenchymal transition.[2][3] Additionally, αvβ6-mediated TGF-β1 activation within the tumor microenvironment promotes angiogenesis, cancer-associated fibroblast activation, and immune suppression, all contributing to cancer progression.[3] Because αvβ6 is minimally expressed in healthy adult tissues but upregulated during wound healing, tissue remodeling, fibrosis, and malignant transformation, it represents an attractive target for cancer-selective therapeutics with potentially limited off-target toxicity.[3] Therapeutic approaches including αvβ6-targeting antibodies and immunoliposomes have demonstrated the ability to inhibit tumor growth, reduce cancer cell migration, and induce apoptosis in preclinical studies.[2]

Other names

Integrin beta-6ITGB6 (gene name for the β6 subunit)Integrin alpha-V:beta-6

TGF-β1 activation through binding of latency-associated peptide (LAP); Fibronectin and cytactin binding via recognition of RGD motif; MAP kinase pathway activation promoting cancer progression; ERK and Akt phosphorylation increasing cell proliferation and survival; Matrix metalloproteinase (MMP) secretion promoting extracellular matrix degradation; Clathrin-mediated and caveolin-mediated endocytosis for ligand internalization