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The E-cadherin-repressed hNanos1 gene induces tumor cell invasion by upregulating MT1-MMP expression

Oncogene volume 27, pages 3692–3699 (2008)Cite this article

Abstract

In this study, we examined the role of the E-cadherin-repressed gene human Nanos1 (hNanos1) in tumor invasion process. First, our in vivo study revealed that hNanos1 mRNAs were overexpressed in invasive lung carcinomas. Moreover, hNanos1 was co-localized with MT1-MMP (membrane type 1-matrix metalloproteinase) in E-cadherin-negative invasive lung tumor clusters. Using an inducible Tet-on system, we showed that induction of hNanos1 expression in DLD1 cells increased their migratory and invasive abilities in a three-dimensional migration and in a modified Boyden chamber assay. Accordingly, we demonstrated that hNanos1 upregulated MT1-MMP expression at the mRNA and protein levels. Inversely, using an RNA interference strategy to inhibit hNanos1 expression in invasive Hs578T, BT549 and BZR cancer cells, we observed a downregulation of MT1-MMP mRNA and protein and concomitantly a decrease of the invasive capacities of tumor cells in a modified Boyden chamber assay. Taken together, our results demonstrate that hNanos1, by regulating MT1-MMP expression, plays an important role in the acquisition of invasive properties by epithelial tumor cells.

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Acknowledgements

This work was supported by grants from the Lions Club of Soissons, Ligue Contre le Cancer, Région Champagne-Ardenne, Fond National pour la Santé ACI 2004-2010 INCa (Cancéropôle Grand-Est project), CGRI-FNRS-INSERM coopération, Fund for Scientific Research (FWO)-Flanders, Interuniversity Attraction Poles Programme of the Belgian Science Policy, Association for International Cancer Research (AICR-UK) and Belgian Federation against Cancer. KS was supported by the Instituut voor de aanmoediging van Innovatie door Wetenschap en Technologie in Vlaanderen (IWT-Flanders) and by a young scientist scholarship of the Centrum voor de studie en behandeling van gezwelziekten, Ghent-Flanders. GB is a postdoctoral fellow with the FWO.

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Authors and Affiliations

  1. INSERM UMRS 514, Laboratory of Histology, IFR 53, CHU Maison Blanche, University of Reims Champagne-Ardenne, Reims, France

    A Bonnomet, M Polette, V Dalstein, C Kileztky, P Birembaut & B Nawrocki-Raby

  2. Laboratory of Developmental and Tumor Biology, University of Liège, CHU Sart-Tilman, Liège, Belgium

    A Bonnomet & C Gilles

  3. Department for Molecular Biomedical Research, VIB-Ghent University, Ghent, Belgium

    K Strumane, G Berx & F van Roy

  4. Department IHB, Leiden University Medical Centre, Leiden, The Netherlands

    K Strumane

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  1. A Bonnomet
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  2. M Polette
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  3. K Strumane
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  4. C Gilles
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Correspondence to B Nawrocki-Raby.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Bonnomet, A., Polette, M., Strumane, K. et al. The E-cadherin-repressed hNanos1 gene induces tumor cell invasion by upregulating MT1-MMP expression. Oncogene 27, 3692–3699 (2008). https://doi.org/10.1038/sj.onc.1211035

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