Because of the important role of EMT in cancer progression, we hypothesized that alcohol abuse may worsen the outcome of epithelial-derived cancers such as colon and breast cancer, by stimulating EMT in cancer cells and thus promoting cancer progression and metastases. The aim of our study was to test our hypothesis by determining if alcohol, at relevant in vivo levels, stimulates key phenotypic and functional signatures of EMT associated with cancer progression in colon and breast cancer cell lines as well as in a nontransformed (normal) intestinal epithelial cell line. We also sought to investigate the signaling mechanism of alcohol-induced promotion of EMT. To this end, we determined the effects of alcohol on activation and mRNA expression of the key EMT Snail transcription factor as well as upstream signaling pathways related to EGFR signaling that might be turning on Snail and EMT. Also, in order to determine the potential relevance of our in vitro findings, we measured Snail mRNA expression in sigmoid colon mucosal samples from alcoholic subjects.
