The integrin α6β4 and the biology of carcinoma

Abstract

The integrin family of adhesion receptors plays a major role in epithelial organization and function. Moreover, the altered expression and function of specific integrins most likely contributes significantly to carcinoma progression. The integrin α6β4, the focus of this review, is a receptor for several members of the laminin family and is preferentially expressed at the basal surface of most epithelia, where it contributes to basement membrane interactions. Mounting evidence suggests that the α6β4 integrin plays a key role in carcinoma cell biology. Several histopathological studies have established a correlation between α6β4 integrin expression and tumor progression. The importance of α6β4 expression in tumors is underscored by the findings that invading fronts of several carcinomas are enriched in the expression of α6β4 integrin ligands, such as laminin-1 and laminin-5. The participation of the α6β4 integrin in invasion is supported further by in vitro functional studies using carcinoma cells that have been transfected with the β4 cDNA. The mechanisms by which α6β4 contributes to tumor progression are probably related to its mechanical and signaling properties and are currently under intense study.Key words: integrins, laminin receptors, basement membrane, extracellular matrix, metastasis.