Abstract
The zinc finger transcription factor, Snail, functions as a potent repressor of E-cadherin expression that can induce an epithelial-mesenchymal transition (EMT). Down-regulation of E-cadherin is thought to play a major role in the abnormal manifestation of EMT in epithelial-derived cancer types. Wnt signaling can also induce EMT and impact on multiple cell functions in neoplastic tissues. Although Wnt signaling could conceivably stabilize the pool of cytosolic β-catenin that is released from E-cadherin-bound sites as a consequence of Snail-mediated E-cadherin repression, direct interplay between the Wnt and Snail systems has remained a subject of conjecture. We demonstrate that Wnt-1 induces the up-regulation of endogenous levels of nuclear Snail protein as well as those of β-catenin, coupled with its ability to repress E-cadherin expression and support a tissue invasive EMT program. These data suggest that Wnt signaling stabilizes Snail and β-catenin proteins in tandem fashion so as to induce cancer invasion and metastasis via EMT program.
