Knockout of α6β1-integrin expression reverses the transformed phenotype of hepatocarcinoma cells

Background & Aims: Hepatocellular carcinoma is a common complication in liver cirrhosis. The integrin alpha 6 beta 1, a receptor for the laminin family of extracellular matrix proteins, has been found to be overexpressed in hepatocarcinoma. In an effort to further characterize the involvement of alpha 6 beta 1-integrin in hepatocarcinoma progression and to study alpha 6 beta 1-mediated functions, a human hepatocarcinoma cell line, HepG2, that express high surface levels of alpha 6 beta 1 and uses only this integrin to mediate adhesion on laminin was identified. Methods: To assess the role of alpha 6 beta 1 in these cells, a cytoplasmic domain deletion mutant of the beta 4-integrin subunit by complementary DNA transfection was expressed. The expression of the mutant beta 4 subunit in association with endogenous alpha 6 showed a dominant-negative effect on alpha 6 beta 1 expression. Results: Stable transfectants of HepG2 that expressed the mutant beta 4 subunit showed a reduced ability to adhere and migrate on laminin matrices and to invade Matrigel. Furthermore, transfected cells showed significantly lower growth rates and reduced anchorage-independent growth compared with mock-transfected cells. Conclusions: These findings on the expression and function of alpha 6 beta 1 in hepatocarcinoma cells emphasize the potential contribution of this laminin receptor in the neoplastic transformation of hepatocytes.