In this study, we found that inhibition of activity of proprotein convertases (PCs) in human primary melanoma cells with altered p53, CDKN2A and Ras genes, provides a potent repression mechanism of primary melanoma cell invasiveness by interfering with the expression and/or activity of several extracellular matrix degrading enzymes and their inhibitors. The gene discussed is CNTN3; the disease is melanoma.