Our data for both breast and colon cancer cells shows that alcohol stimulates nuclear localization and phosphorylation of Snail at Ser246, probably by PAK1(Yang et al., 2005). In addition we show alcohol stimulates mRNA expression from a Snail reporter plasmid and Snail mRNA expression in colon and breast cancer cell lines. Snail has been called a master regulator of EMT (Peinado et al., 2007). A hierarchical model of transcriptional regulation of EMT involves other key transcription factors that have been identified including Snail2, ZEB1/2, and Twist but places Snail at the top of this hierarchy (Peinado et al., 2007). Overexpression of Snail alone is sufficient to induce EMT in cell lines in vitro (Cano et al., 2000, Julien et al., 2007) and recently to generate possible cancer stem cells (Mani et al., 2008). In transgenic mice, chronic Snail activation results in multiple epithelial and mesenchymal tumors (Perez-Mancera et al., 2005). In another mouse model, Snail expression determined breast cancer invasiveness and recurrence (Moody et al., 2005). Overexpression of Snail has also been shown to correlate closely with invasiveness and recurrence
