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The transcription factor Snail is a repressor of E-cadherin gene expression in epithelial tumour cells

Nature Cell Biology volume 2, pages 84–89 (2000)Cite this article

Abstract

The adhesion protein E-cadherin plays a central part in the process of epithelial morphogenesis. Expression of this protein is downregulated during the acquisition of metastatic potential at late stages of epithelial tumour progression. There is evidence for a transcriptional blockage of E-cadherin gene expression in this process. Here we show that the transcription factor Snail, which is expressed by fibroblasts and some E-cadherin-negative epithelial tumour cell lines, binds to three E-boxes present in the human E-cadherin promoter and represses transcription of E-cadherin. Inhibition of Snail function in epithelial cancer cell lines lacking E-cadherin protein restores the expression of the E-cadherin gene.

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Figure 1: Snail expression inversely correlates with E-cadherin mRNA levels.
Figure 2: Exogenous expression of mmSna downregulates E-cadherin mRNA levels.
Figure 3: Antisense repression of Snail mRNA restores E-cadherin expression.
Figure 4: mmSna blocks the activity of the –178/+92 fragment of the human E-cadherin promoter.
Figure 5: Mutation of the E-boxes impairs repression of the E-cadherin promoter by Snail.
Figure 6: Snail binds to the three E-boxes present in the –178/+92 fragment of the human E-cadherin promoter.

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Acknowledgements

We thank M. Garrido and C. Torns for technical help; J. Lloreta for assistance with electron microscopy; S. Gómez and S. Guaita for purification of fusion proteins; A. Fabra and F. Ulloa for reagents; R. Romero and D. Bueno for help with microscopy; F.X. Real for reagents, support and discussions during the study; and C. de Bolòs, M. Vilà and A. Meseguer for help in some critical moments. This work was supported by grants SAF 97-080 from Comisión Interministerial de Ciencia y Tecnología (CICYT) and from La Marató de TV3 to A.G.H. E.B. was supported by a predoctoral fellowship from CIRIT (Generalitat de Catalunya), and E.S. by funding from La Marató de TV3. J.B. was a recipient of a postdoctoral contract from the Ministerio de Educación.

Correspondence and requests for materials should be addressed to A.G.H. The human Snail cDNA sequence has been deposited in GenBank under accession number AF131208.

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  1. Eduard Batlle and Elena Sancho: These authors contributed equally to this work

Authors and Affiliations

  1. Unitat de Biologia Cel.lular i Molecular, Institut Municipal d’Investigació Mèdica, Universitat Pompeu Fabra, Dr Aiguader 80, Barcelona, 08003 , Spain

    Eduard Batlle, Elena Sancho, Clara Francí, David Domínguez, Mercè Monfar, Josep Baulida & Antonio García de Herreros

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  1. Eduard Batlle
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Correspondence to Antonio García de Herreros.

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Batlle, E., Sancho, E., Francí, C. et al. The transcription factor Snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol 2, 84–89 (2000). https://doi.org/10.1038/35000034

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