In this study, we have attempted to elucidate the expression and function of CD151 in human salivary gland cancer cells. CD151 expression was detected in Acc2 and AccM cells, but not in normal tissues and primary cultured epithelial cells derived from human salivary gland. CD151 has been found to function as a molecular linker in the formation of complexes between c-Met/hepatocyte growth factor (HGF) receptor and integrin alpha3/alpha6. Knockdown of CD151 or integrin alpha3/alpha6 expression almost completely abrogated HGF-stimulated cell growth and migration. In contrast, forced expression of CD151 in Acc2 cells resulted in the increase of the HGF-dependent biological effects. These results suggest that CD151 forms a structural and functional complex with c-Met and integrin alpha3/alpha6, and exerts its oncogenic functions through excessive activation of the HGF/c-Met signalling pathway.