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Regulation of vimentin by SIP1 in human epithelial breast tumor cells

Oncogene volume 25, pages 4975–4985 (2006)Cite this article

Abstract

The expression of Smad interacting protein-1 (SIP1; ZEB2) and the de novo expression of vimentin are frequently involved in epithelial-to-mesenchymal transitions (EMTs) under both normal and pathological conditions. In the present study, we investigated the potential role of SIP1 in the regulation of vimentin during the EMT associated with breast tumor cell migration and invasion. Examining several breast tumor cell lines displaying various degrees of invasiveness, we found SIP1 and vimentin expression only in invasive cell lines. Also, using a model of cell migration with human mammary MCF10A cells, we showed that SIP1 is induced specifically in vimentin-positive migratory cells. Furthermore, transfection of SIP1 cDNA in MCF10A cells increased their vimentin expression both at the mRNA and protein levels and enhanced their migratory abilities in Boyden Chamber assays. Inversely, inhibition of SIP1 expression by RNAi strategies in BT-549 cells and MCF10A cells decreased vimentin expression. We also showed that SIP1 transfection did not activate the TOP-FLASH reporter system, suggesting that the β-catenin/TCF pathway is not implicated in the regulation of vimentin by SIP1. Our results therefore implicate SIP1 in the regulation of vimentin observed in the EMT associated with breast tumor cell migration, a pathway that may contribute to the metastatic progression of breast cancer.

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Acknowledgements

We thank Dr H Clevers for the TOP-FLASH, the FOP-FLASH and TCF-4 expression vector and Dr K Orford and Dr S Byers for the β-catenin expression vector. This work was supported by grants from the ‘Communauté française de Belgique (Actions de Recherches Concertées)’, the Commission of European Communities (European Union Framework Programs 5 and 6, BRECOSM), the ‘Fonds de la Recherche Scientifique Médicale’, the ‘Fonds National de la Recherche Scientifique’ (FNRS, Belgium), the ‘Fédération Belge Contre le Cancer’, the ‘coopération C.G.R.I.-F.N.R.S.-INSERM’, the ‘Fonds spéciaux de la Recherche (University of Liège), the ‘Centre Anticancéreux près l'Université de Liège’, the Fortis Banque Assurances, the ‘Fondation Léon Fredericq’ (University of Liège), the D.G.T.R.E. from the ‘Région Wallonne’, the ‘Fonds d'Investissements de la Recherche Scientifique (CHU, Liège, Belgium)’, the Interuniversity Attraction Poles Program – Belgian Science Policy (Brussels, Belgium). CG is a Research Associate from the FNRS (Belgium), SB is an FRIA grant holder from the F.N.R.S., MM is a Research Fellow from the F.N.R.S, and GB is a postdoctoral researcher with the FWO (Belgium).

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Authors and Affiliations

  1. Laboratory of Tumor and Developmental Biology, Center for Biomedical Integrated Genoproteomics, University of Liège, CHU Sart-Tilman, Liège, Belgium

    S Bindels, M Mestdagt, L Volders, A Noël, J-M Foidart & C Gilles

  2. Department for Molecular Biomedical Research, VIB-Ghent University, Ghent (Zwijnaarde), Belgium

    C Vandewalle, F van Roy & G Berx

  3. Laboratory of Anatomopathology, Center for Biomedical Integrated Genoproteomics, University of Liège, CHU Sart-Tilman, Liège, Belgium

    N Jacobs

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  1. S Bindels
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Correspondence to C Gilles.

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Bindels, S., Mestdagt, M., Vandewalle, C. et al. Regulation of vimentin by SIP1 in human epithelial breast tumor cells. Oncogene 25, 4975–4985 (2006). https://doi.org/10.1038/sj.onc.1209511

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