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Fhit regulates invasion of lung tumor cells

Oncogene volume 29, pages 1203–1213 (2010)Cite this article

Abstract

In many types of cancers, the fragile histidine triad (Fhit) gene is frequently targeted by genomic alterations leading to a decrease or loss of gene and protein expression. Fhit has been described as a tumor suppressor gene because of its ability to induce apoptosis and to inhibit proliferation of tumor cells. Moreover, several studies have shown a correlation between the lack of Fhit expression and tumor aggressiveness, thus suggesting that Fhit could be involved in tumor progression. In this study, we explored the potential role of Fhit during tumor cell invasion. We first showed that a low Fhit expression is associated with in vivo and in vitro invasiveness of tumor cells. Then, we showed that Fhit overexpression in Fhit-negative highly invasive NCI-H1299 cells by transfection of Fhit cDNA and Fhit inhibition in Fhit-positive poorly invasive HBE4-E6/E7 cells by transfection of Fhit small interfering RNA induce, respectively, a decrease and an increase in migratory/invasive capacities. These changes in cell behavior were associated with a reorganization of tight and adherens junction molecules and a regulation of matrix metalloproteinase and vimentin expression. These results show that Fhit controls the invasive phenotype of lung tumor cells by regulating the expression of genes associated with epithelial–mesenchymal transition.

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Acknowledgements

This study was supported by the Région Champagne-Ardenne, the Ligue Contre le Cancer (Comité de la Marne), the Lions Club of Soissons, Un Euro contre le Cancer and the Fond National pour la Santé ACI 2004–2010 INCa (Cancéropôle Grand-Est project).

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Authors and Affiliations

  1. INSERM, U903, Reims, France

    A Joannes, M Polette, H Burlet, J Cutrona, J-M Zahm, P Birembaut & B Nawrocki-Raby

  2. Univ Reims Champagne Ardenne, IFR53, UMR-S903, Reims, France

    A Joannes, M Polette, H Burlet, J-M Zahm, P Birembaut & B Nawrocki-Raby

  3. Univ Liège, CHU Sart-Tilman, Laboratoire de Biologie des Tumeurs et du Développement, Liège, Belgium

    A Bonnomet, S Bindels & C Gilles

  4. CHU Reims, Hôpital Maison Blanche, Laboratoire Pol Bouin, Reims, France

    M Polette & P Birembaut

  5. Univ Reims Champagne Ardenne, CRESTIC, Reims, France

    J Cutrona

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  1. A Joannes
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  2. A Bonnomet
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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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Joannes, A., Bonnomet, A., Bindels, S. et al. Fhit regulates invasion of lung tumor cells. Oncogene 29, 1203–1213 (2010). https://doi.org/10.1038/onc.2009.418

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