The Met receptor and α₆β₄ integrin can function independently to promote carcinoma invasion

It has been proposed that a constitutive, physical association of the Met receptor and the α₆β₄ integrin exists on the surface of invasive carcinoma cells and that hepatocyte growth factor (HGF)-mediated invasion is dependent on α₆β₄ (Trusolino, L., Bertotti, A., and Comoglio, P. M. (2001) Cell 107, 643-654). The potential significance of these results prompted us to re-examine this hypothesis. Using three different carcinoma cell lines that express both Met and α₆β₄, we were unable to detect the constitutive association of these receptors by co-immunoprecipitation. Moreover, carcinoma cells that lacked expression of α₆β₄ exhibited Met-dependent invasion toward HGF, and increasing Met expression by viral infection of these cells enhanced invasion without inducing α₆β₄ expression. Although expression of α₆β₄ in such cells enhanced their invasion to HGF, it also enhanced their ability to invade toward other chemoattractants such as lysophosphatidic acid, and this latter invasion was not inhibited by a function-blocking Met antibody. Finally, depletion of β₄ by RNA interference in invasive carcinoma cells that express both receptors reduced the ability of these cells to invade toward HGF by ∼25%, but it did not abrogate their invasion. These data argue that the invasive function of Met can be independent of α₆β₄ and that α₆β₄ has a generic influence on the invasion of carcinoma cells that is not specific to Met.