Background: Previous reports have demonstrated that SNAI1 plays a role in epithelial-mesenchymal transition (EMT) through the suppression of CDH1. Its role in the pathology and regulation of EMT expression to chemoresistance in colorectal cancer (CRC) has not yet been fully elucidated. Methods: Immunohistochemistry was performed to evaluate the expression of Snail protein in 30 primary CRC samples. The biological significance of Snail expression was studied by induction of the wild-type (WT) and mutant SNAI1 gene in CRC SW480 cells. Results: Examination of 20 surgical specimens of CRC indicated that Snail protein expression was localized outer regions of invasive tumors. Introduction of phosphorylation-defective active EMT forms, SNAI1-6SA and SNAI1-8SA, caused downregulation of CDH1 and upregulation of VIM compared with SNAI1-WT and the negative control (NC). Chemoresistance to 5-fluorouracil (IC50) was higher in SNAI1-6SA and SNAI1-8SA transfectants compared with SNAI1-WT and NC. All the above results were significantly different. Conclusion: The present study demonstrated that Snai1 plays a role in CRC invasion through phosphorylation, suggesting a plausible mechanism for overcoming chemoresistance that will lead to the development of effective treatments for CRC. (C) 2009 Elsevier Inc. All rights reserved.