Although treatment with recombinant CR-1 and Nodal only slightly enhanced the activation of Smad-2 in melanoma cells, blockade of ALK activation with a specific inhibitor was able to significantly reduce the ability of CR-1 to stimulate melanoma cell invasion, suggesting that Nodal/Smad-2 signalling has an important role in CR-1-induced invasiveness. This evidence concerns the gene SMAD2 and melanoma.