A function for the integrin α₆β₄ in the invasive properties of colorectal carcinoma cells

Expression of the integrin α₆β₄, a receptor for the laminin family of matrix proteins, has been correlated with the progression and metastatic potential of several different tumors, including colorectal carcinoma. For this reason, defining the mechanistic contribution of α₆β₄ to the aggressive behavior of colorectal and other carcinoma cells is an issue of timely importance for cancer biology. In the present study, we sought to gain insight into the function of α₆β₄ in colorectal carcinoma cells by studying the behavior of clone A cells, which express high surface levels of this integrin, and by restoring α₆β₄ expression in RKO cells, a β₄- deficient rectal carcinoma cell line. The data obtained reveal that α₆β₄ expression increases the adhesive strength of these cells on laminin-1 matrices, although it does not increase their ability to migrate on such matrices. The RKO/β₄ transfectants were considerably more spread on Matrigel, laminin-1, and collagen I than the mock transfectants and displayed numerous extensions suggestive of pseudopodia. More importantly, we discovered that expression of α₆β₄ facilitates the ability of colorectal carcinoma cells to invade both Matrigel and collagen I matrices. The α₆β₄-dependent increases in adhesion and invasion, as well as the observed morphological changes, required an intact β₄ cytoplasmic domain. These data argue for a ligand-independent role for α₆β₄ in promoting cell invasion, and they have important implications for the involvement of this integrin in colorectal carcinoma progression.