Abstract: Objective To characterize the mechanism of NDRG1-induced colon cancer aggressiveness including NDRG1-induced colon cancer cell migration and invasion. Methods HT-29 human colorectal cell，was employed to detect cell migration and invasion using transwell assays.The role of ERK in NDRG1-mediated cell migration and invasion was also evaluated by employing the MEK/ERK inhibitor.Change of cell morphology was microscopically examined.Transmission electron microscope was also used to examine the effect of ERK inhibitor on HT-29 ultra structure change. Results Treatment with ERK inhibitor changed HT-29 cell morphology.The size，appearance of the cells and nuclei were inclined with uniformity；the arrangement of the cells was glandule-like texture.There were more microvilli on the cell surface and the numbers of Golgi complexes，mitochondria were increasing；there were also more rough endoplasmic reticula；intracytoplasmic lumen was frequently seen；cells treated with ERK inhitors also induced cell apoptosis.Comparing with control groups，cell migratory ability was significantly inhibited by the inhibitors.Using an immunocytochemical staining approach，we demonstrated that increased NDRG1 protein was elevated in cells treated with the inhibitors，than that in control cells.Western blot confirmed this observation. Conclusion Our data indicate that blocking the MAPK pathway induces differentiation and apoptosis of the HT-29 colorectal cancer cells.In addition，inhibition of MAPK pathway also suppresses cancer cell invasive/migratory abilities through up-regulation of NDRG1 protein.