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The intestine-specific homeobox gene Cdx2 decreases mobility and antagonizes dissemination of colon cancer cells

Oncogene volume 27, pages 107–115 (2008)Cite this article

Abstract

The gravity of colorectal cancer is mainly due to the capacity of tumor cells to migrate out of the tumor mass to invade the stroma and disseminate as metastases. The acquisition of a migratory phenotype also occurs during wound healing. Here, we show that several features characterizing invasive colon tumor cells are shared by migrating cells during wound repair in vitro. In particular, the expression of the intestine-specific transcription factor Cdx2, a key gene for intestinal identity downregulated in invasive cancer cells, is reduced during wound healing in vitro. Transcription factors involved in epithelial–mesenchymal transition such as Snail and Slug are upregulated during wound healing and are able to repress Cdx2 transcription. In vitro, forced expression of Cdx2 in human colon cancer cell lines retarded wound repair and reduced migration, whereas inhibition of Cdx2 expression by RNA interference enhanced migration. In vivo, forced expression of Cdx2 opposed tumor cells spreading in nude mice xenografted at three different sites. These data provide evidence that Cdx2 antagonizes the process of tumor cell dissemination, and they suggest that this homeobox gene might represent a new therapeutic target against metastatic spreading of colon cancer.

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Acknowledgements

We thank Drs M Rousset, P Simon-Assmann, P Jay, P Savagner, AG de Herreros and A Postigo for antibodies, plasmids and cells. We acknowledge M Yahya (IUT Louis Pasteur, Strasbourg) for excellent technical assistance. This work was supported at U.682 by INSERM, the Fond National pour la Santé (ACI 2004, Cancéropôle Grand-Est) and the Institut National du Cancer (AO 2006). IG is a fellow of the Institut National du Cancer (Cancéropôle Grand-Est) and AC of the Ligue Régionale Contre le Cancer (Haut-Rhin and Bas-Rhin, France).

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Authors and Affiliations

  1. INSERM, U682, Strasbourg, France

    I Gross, I Duluc, T Benameur, A Calon, E Martin, M Kedinger, C Domon-Dell & J-N Freund

  2. Faculté de Médecine, Université Louis Pasteur, Strasbourg, France

    I Gross, I Duluc, T Benameur, A Calon, E Martin, M Kedinger, C Domon-Dell & J-N Freund

  3. Department of Surgery, University of Freiburg, Freiburg, Germany

    T Brabletz

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Correspondence to J-N Freund.

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

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Gross, I., Duluc, I., Benameur, T. et al. The intestine-specific homeobox gene Cdx2 decreases mobility and antagonizes dissemination of colon cancer cells. Oncogene 27, 107–115 (2008). https://doi.org/10.1038/sj.onc.1210601

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