This is the first report to functionally link two metastasis-associated genes, MACC1 and S100A4, and to elucidate their cooperation as inducer (MACC1) and enforcer (S100A4) of CRC cell motility and metastasis in one functionally shared MACC1-β-catenin-S100A4 axis. This evidence concerns the gene MACC1 and colorectal carcinoma.