In summary, collectively our data present evidence for a novel pathway for alcohol promotion of cancer progression through induction of the EMT gene program in cancer cells. To our knowledge these data are the first to show that alcohol activates and increases mRNA expression of the key EMT transcription factor Snail or to show EGFR transactivation and induction of MMPs by alcohol in epithelial cells. Together with the vimentin, E-cadherin reporter, and cell migration [a surrogate marker for metastasis] data our study strongly supports the hypothesis that alcohol induces the EMT program in cancer cells and promotes metastasis. The mechanisms for exactly how EMT promotes cancer progression are currently being unraveled. Future studies will be needed to identify the individual roles of EGFR, MMP, and Snail signaling in alcohol induction of EMT as well as the possible roles for other EMT transcription factors. Identification of this novel mechanism for alcohol promotion of cancer progression could open new avenues for prevention and treatment of alcohol-related cancers.
