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[Cancer Research 65, 6237-6244, July 15, 2005]
© 2005 American Association for Cancer Research

Cell and Tumor Biology

The Transcription Factor Snail Induces Tumor Cell Invasion through Modulation of the Epithelial Cell Differentiation Program

Bram De Craene1, Barbara Gilbert1, Christophe Stove1,2, Erik Bruyneel3, Frans van Roy2 and Geert Berx1

1 Unit of Molecular and Cellular Oncology and 2 Molecular Cell Biology Unit, Department for Molecular Biomedical Research, VIB-Ghent University; and 3 Laboratory of Experimental Cancerology, University Hospital of Ghent, Ghent, Belgium

Requests for reprints: Geert Berx, Department for Molecular Biomedical Research, Unit of Molecular and Cellular Oncology, Technologiepark 927, B-9052 Ghent (Zwijnaarde), Belgium. Phone: 32-9-33-13-740; Fax: 32-9-33-13-609; E-mail: Geert.Berx{at}dmbr.UGent.be.

Abberant activation of the process of epithelial-mesenchymal transition in cancer cells is a late event in tumor progression. A key inducer of this transition is the transcription factor Snail, which represses E-cadherin. We report that conditional expression of the human transcriptional repressor Snail in colorectal cancer cells induces an epithelial dedifferentiation program that coincides with a drastic change in cell morphology. Snail target genes control the establishment of several junctional complexes, intermediate filament networks, and the actin cytoskeleton. Modulation of the expression of these genes is associated with loss of cell aggregation and induction of invasion. Chromatin immunoprecipitation experiments showed that repression of selected target genes is associated with increased binding of Snail to their promoters, which contain consensus Snail-binding sites. Thus, Snail constitutes a master switch that directly represses the epithelial phenotype, resulting in malignant carcinoma cells.




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Copyright © 2005 by the American Association for Cancer Research.