Cell lines were screened for secretion of cystatin E/M and C, as well as expressions of legumain, cathepsin B and L. We found that cystatin E/M, legumain, cathepsin B and L were expressed in several of these melanoma cell lines and that over-expression of cystatin E/M resulted in inhibition of legumain activity and decreased invasiveness. Here, CST6 is linked to melanoma.