Abstract
G A A b st ra ct s this Snail phosphorylation and nuclear localization. In addition, we show that a chemical inhibitor of iNOS as well as siRNA iNOS knockdown prevent activation of Snail by alcohol. Finally, we show that at rest, Snail is associated with Flotillin-2 membrane rafts while iNOS is associated with Caveolin-1 rafts. PAK1 is not associated with the membrane rafts. Upon stimulation PAK1 is translocated to Flotillin-2 rafts along with iNOS and Snail and activated Snail is translocated to the nucleus. Conclusions. Our data support a mechanism is which Flotillin-2 membrane rafts form a signaling platform for alcohol-induced activation of Snail via iNOS and PAK1.These are the first data to show iNOS activation of PAK1 and Snail and Snail association with membrane rafts by any stimulus and provide new insight into mechanisms regulating EMT as well as mechanisms through which alcohol may promote colon cancer progression through EMT that could be targeted for therapy.
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