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Regulation of Snail transcription during epithelial to mesenchymal transition of tumor cells

Oncogene volume 23, pages 7345–7354 (2004)Cite this article

Abstract

Expression of Snail transcriptional factor is a determinant in the acquisition of a mesenchymal phenotype by epithelial tumor cells. However, the regulation of the transcription of this gene is still unknown. We describe here the characterization of a human SNAIL promoter that contains the initiation of transcription and regulates the expression of this gene in tumor cells. This promoter was activated in cell lines in response to agents that induce Snail transcription and the mesenchymal phenotype, as addition of the phorbol ester PMA or overexpression of integrin-linked kinase (ILK) or oncogenes such as Ha-ras or v-Akt. Although other regions of the promoter were required for a complete stimulation by Akt or ILK, a minimal fragment (−78/+59) was sufficient to maintain the mesenchymal specificity. Activity of this minimal promoter and SNAIL RNA levels were dependent on ERK signaling pathway. NFκB/p65 also stimulated SNAIL transcription through a region located immediately upstream the minimal promoter, between −194 and −78. These results indicate that Snail transcription is driven by signaling pathways known to induce epithelial to mesenchymal transition, reinforcing the role of Snail in this process.

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Acknowledgements

This work was supported by Grants from Fundación Científica de la Asociación Española contra el Cáncer and Ministerio de Ciencia y Tecnología (PM99-0132 and SAF2003-02324) to AGH and by a grant from FEGEFLUC to LL. Partial support from a grant from Instituto Carlos III (RTICCC, C03710) is also appreciated. We thank Drs C Caelles, M Fresno, P Crespo, HG Pálmer and F Posas for the reagents. SG and IP are recipients of predoctoral fellowships from Ministerio de Ciencia y Tecnología and Ministerio de Educación, respectively. DD was a fellow from Instituto de Salud Carlos III. We are grateful to Dr Eduard Batlle for his initial work on the isolation of the promoter. The technical support of Judit Grueso is greatly appreciated.

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Author notes

  1. Maria José Barberà

    Present address: Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Canada

  2. Maria José Barberà, Isabel Puig and David Domínguez: MJB, IP and DD contributed equally to this work and should be considered as co-first authors.

  3. David Domínguez: Currently works at the Institute for Cancer Genetics, Columbia University, New York, USA.

Authors and Affiliations

  1. Unitat de Biologia Cellular i Molecular, Institut Municipal d'Investigació Mèdica, Universitat Pompeu Fabra, Barcelona, Spain

    Maria José Barberà, Isabel Puig, David Domínguez, Sandra Guaita-Esteruelas, Sandra Peiró, Josep Baulida, Clara Francí & Antonio García de Herreros

  2. Developmental Genetics of Melanocytes, UMR146, CNRS-Institut Curie, Orsay Cedex, 91405, France

    Sylvia Julien-Grille & Lionel Larue

  3. Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, V6H 3Z6, British Columbia, Canada

    Shoukat Dedhar

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Correspondence to Antonio García de Herreros.

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Barberà, M., Puig, I., Domínguez, D. et al. Regulation of Snail transcription during epithelial to mesenchymal transition of tumor cells. Oncogene 23, 7345–7354 (2004). https://doi.org/10.1038/sj.onc.1207990

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