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J. Biol. Chem., Vol. 277, Issue 42, 39209-39216, October 18, 2002
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From the E-cadherin protein plays a key role in the
establishment and maintenance of adherent junctions. Recent
evidence implicates the transcription factor Snail in the blockage of
E-cadherin expression in fibroblasts and some epithelial tumor cells
through direct binding to three E-boxes in the E-cadherin promoter.
Transfection of Snail into epithelial cells leads to a more
fibroblastic phenotype. Cells expressing Snail presented a scattered
flattened phenotype with low intercellular contacts. Other
epithelial markers like Cytokeratin 18 or MUC1 were also repressed. The
effects of Snail on MUC1 transcription were mediated by two E-boxes
present in the proximal promoter. Snail also induced expression of
the mesenchymal markers fibronectin and LEF1 and the transcription
repressor ZEB1. ZEB1 and Snail had a similar pattern of expression in
epithelial cell lines, and both were induced by overexpression of ILK1,
a kinase that causes the loss of E-cadherin and the acquisition of a
fibroblastic phenotype. Snail overexpression in several cell lines
raised ZEB1 RNA levels and increased the activity of ZEB1 promoter.
ZEB1 could also repress E-cadherin and MUC1 promoters but less
strongly than Snail. However, since ZEB1 expression persisted after
Snail was down-regulated, ZEB1 may regulate epithelial genes in several
tumor cell lines.
Snail Induction of Epithelial to Mesenchymal Transition in Tumor
Cells Is Accompanied by MUC1 Repression and
ZEB1 Expression*
§¶,
§
,
,
,
,
**,
**,
,
§§, and
¶¶
Unitat de Biologia Cellular i Molecular,
Institut Municipal d'Investigació Mèdica, Universitat
Pompeu Fabra, E-08003 Barcelona, Spain and the

Department of Biochemistry and Molecular
Biology, University of British Columbia, Vancouver, British Columbia
V6H 3Z6, Canada
*
This work was supported by Ministerio de Ciencia y
Tecnología Grant PM99-0132 (to A. G. H.) and Fondo de
Investigaciones Sanitarias Grant 01/3060 (to J. B.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Recipient of a predoctoral fellowship from Ministerio de
Educación (Formacion del Profesorado Universitario).
§§
To whom correspondence may be addressed: Institut Municipal
d'Investigació Mèdica, c/Doctor Aiguader, 80, E-08003
Barcelona, Spain. Tel.: 34-93-221-1009; Fax: 34-93-221-3237; E-mail:
agarcia@imim.es.
¶¶
To whom correspondence may be addressed: Institut
Municipal d'Investigació Mèdica, c/Doctor Aiguader, 80, E-08003 Barcelona, Spain. Tel.: 34-93-221-1009; Fax: 34-93-221-3237;
E-mail: jbaulida@imim.es.
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