The integrin alpha 6 beta 4 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 alpha 6 beta 4, 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 alpha 6 beta 4 integrin plays a key role in carcinoma cell biology. Several histopathological studies have established a correlation between alpha 6 beta 4 integrin expression and tumor progression. The importance of alpha 6 beta 4 expression in tumors in underscored by the findings that invading fronts of several carcinomas are enriched in the expression of alpha 6 beta 4 integrin ligands, such as laminin-1 and laminin-5. The participation of the alpha 6 beta 4 integrin in invasion is supported further by in vitro functional studies using carcinoma cells that have been transfected with the beta 4 cDNA. The mechanisms by which alpha 6 beta 4 contributes to tumor progression are probably related to its mechanical and signaling properties and are currently under intense study.