Glycogen synthase kinase-3 is an endogenous inhibitor of Snail transcription: implications for the epithelial-mesenchymal transition

doi:10.1083/jcb.200409067

Published 3 January 2005. doi:10.1083/jcb.200409067
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 168, Number 1, 29-33

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Glycogen synthase kinase-3 is an endogenous inhibitor of Snail transcription : implications for the epithelial–mesenchymal transition

Robin E. Bachelder¹, Sang-Oh Yoon¹, Clara Franci², Antonio García de Herreros², and Arthur M. Mercurio¹

¹ Department of Pathology, Division of Cancer Biology and Angiogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215
² Unitat de Biologia Cellular i Molecular, Institut Municipal d'Investigació Mèdica, Universitat Pompeu Fabra, 08003 Barcelona, Spain

Correspondence to Robin E. Bachelder: rbacheld{at}bidmc.harvard.edu

Abstract
We report that the activity of glycogen synthase kinase-3 (GSK-3)is necessary for the maintenance of the epithelial architecture.Pharmacological inhibition of its activity or reducing its expressionusing small interfering RNAs in normal breast and skin epithelialcells results in a reduction of E-cadherin expression and amore mesenchymal morphology, both of which are features associatedwith an epithelial–mesenchymal transition (EMT). Importantly,GSK-3 inhibition also stimulates the transcription of Snail,a repressor of E-cadherin and an inducer of the EMT. We identifyNF ${kappa}$ B as a transcription factor inhibited by GSK-3 in epithelialcells that is relevant for Snail expression. These findingsindicate that epithelial cells must sustain activation of aspecific kinase to impede a mesenchymal transition.

Abbreviations used in this paper: EMT, epithelial–mesenchymaltransition; GSK-3, glycogen synthase kinase-3; siRNA, smallinterfering RNA.

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