Cancer associated gene (CAGE) regulates expression of epithelial-mesenchymal transition (EMT)-related proteins through extracellular regulated kinase (ERK), Akt and nuclear factor kappa B (NF-kB) in mouse B16F10 melanoma cells. Snail, a EMT-related protein, mediates the effect of CAGE on the induction of matrix metalloproteinase-2 (MMP-2) and cancer cell motility. C-Flice inhibitory protein mediates the effect of CAGE on the induction of MMP-2 and cell motility by the induction of Snail. CAGE was shown to protect cells against celastrol, an anti-cancer agent. Celastrol-resistant B16F10 melanoma cells had a higher expression level of c-FLIPL and Snail as compared with a sensitive cell line.