Integrin αvβ6: Structure, function and role in health and disease

Integrins are cell surface receptors that traditionally mediate cell-to-extracellular matrix and cell-to-cell adhesion. They can, however, also bind a large repertoire of other molecules. Integrin alpha v beta 6 is exclusively expressed in epithelial cells where it can, for example, serve as a fibronectin receptor. However, its hallmark function is to activate transforming growth factor-beta 1 (TGF-beta 1) to modulate innate immune surveillance in lungs and skin and along the gastrointestinal tract, and to maintain epithelial stem cell quiescence. The loss of alpha v beta 6 integrin function in mice and humans leads to an altered immune response in lungs and skin, amelogenesis imperfecta, periodontal disease and, in some cases, alopecia. Elevated alpha v beta 6 integrin expression and aberrant TGF-beta 1 activation and function are associated with organ fibrosis and cancer. Therefore, alpha v beta 6 integrin serves as an attractive target for cancer imaging and for fibrosis and cancer therapy.