Our data suggest that alcohol stimulation of EGFR signaling may promote activation of Snail and EMT. Abnormalities in EGFR signaling or expression are associated with many human cancers (Hynes, 2007). Several different cell signaling pathways have been shown to stimulate induction of EMT including signaling by receptor tyrosine kinases such as the EGFR (Peinado et al., 2007, Thiery and Sleeman, 2006). Chronic stimulation with EGF can result in activation of Snail and EMT(Ackland et al., 2003, Peinado et al., 2007). Blocking EGFR signaling inhibits alcohol-stimulated Snail mRNA expression in our study and Snail mediated colon cancer metastases in mice (Mann et al., 2006). EMT in cervical cancer also correlates with EGFR and Snail overexpression (Lee et al., 2008). Our data suggest alcohol activates EGFR signaling through TACE-mediated transactivation. TACE-mediated EGFR transactivation promotes EMT-mediated cancer progression in breast epithelial cells (Kenny and Bissell, 2007). Our data also show alcohol-stimulated ERK1/2 activation through the EGFR. Overexpression of ERK1/2 also promotes EMT and promoter analysis of Snail reveals a key stimulatory role for ERK1/2 (Barbera et al., 2004, Schramek et al., 2003). In
