Integrin subunit beta 6 (ITGB6)

Integrin subunit beta 6 (ITGB6) is a transmembrane protein that exclusively pairs with the alpha V subunit to form the alpha-v beta-6 (αvβ6) heterodimer [2, 10]. This integrin is primarily expressed on epithelial cells and is significantly upregulated during tissue remodeling, wound healing, and pathological states such as cancer and fibrosis [1, 7]. Its most critical biological function is the mechanical activation of latent transforming growth factor-beta (TGF-β), a potent cytokine that drives fibrogenesis and tumor progression [1, 9]. In oncology, αvβ6 is overexpressed in various solid tumors, including lung, pancreatic, and breast cancers, where it promotes epithelial-mesenchymal transition (EMT), invasion, and metastasis [1, 3, 14]. Therapeutically, ITGB6 is a highly attractive target due to its restricted expression in healthy adult tissues compared to its high density in diseased states [1, 19]. Current drug development efforts include monoclonal antibodies, small molecule inhibitors, and antibody-drug conjugates (ADCs) like sigvotatug vedotin [1, 21]. While targeting this pathway holds promise for treating idiopathic pulmonary fibrosis and metastatic carcinomas, clinical challenges include managing potential on-target toxicities related to the homeostatic roles of TGF-β and the integrin's function in maintaining epithelial integrity [9, 11].

Other names

ITGB6Integrin beta-6AI1HBeta 6 integrin subunit

Inhibition of ligand binding to the alpha-v beta-6 heterodimer, preventing the activation of latent TGF-beta and disrupting downstream pro-tumorigenic and pro-fibrotic signaling pathways [1, 11].