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Nedd9/Hef1/Cas-L mediates the effects of environmental pollutants on cell migration and plasticity

Oncogene volume 28, pages 3642–3651 (2009)Cite this article

Abstract

Aryl hydrocarbon receptor (AhR), or dioxin receptor, is a transcription factor that induces adaptive metabolic pathways in response to environmental pollutants. Recently, other pathways were found to be altered by AhR and its ligands. Indeed, developmental defects elicited by AhR ligands suggest that additional cellular functions may be targeted by this receptor, including cell migration and plasticity. Here, we show that dioxin-mediated activation of Ahr induces Nedd9/Hef1/Cas-L, a member of the Cas protein family recently identified as a metastasis marker. The Hef1 gene induction is mediated by two xenobiotic responsive elements present in this gene promoter. Moreover, using RNA interference, we show that Nedd9/Hef1/Cas-L mediates the dioxin-elicited changes related to cell plasticity, including alterations of cellular adhesion and shape, cytoskeleton reorganization, and increased cell migration. Furthermore, we show that both E-cadherin repression and Jun N-terminal kinases activation by dioxin and AhR also depend on the expression of Nedd9/Hef1/Cas-L. Our study unveils, for the first time, a link between pollutants exposure and the induced expression of a metastasis marker and shows that cellular migration and plasticity markers are regulated by AhR and its toxic ligands.

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Acknowledgements

This work was supported by AFSSET (Agence Française de Sécurité Sanitaire de l’Environnement et du Travail; all authors); ANR (Agence Nationale de la Recherche, 06SEST26, Oncopop; all authors); ARC (Association pour la Recherche sur le Cancer, 3927; all authors); Fondation pour la Recherche Medicale (Bourse postdoctorale, Linh-Chi Bui); INSERM (Institut National de la Santé et de la Recherche Médicale; all authors); Ligue contre le Cancer (Bourse postdoctorale, Linh-Chi Bui); Ministère de l’enseignement supérieur et de la recherche (Bourse doctorale, Aline Chevallier); Région Ile de France (bourse doctorale, Stéphane Pierre); Université Paris Descartes.

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Author notes

  1. C Transy

    Present address: 7Current address: Institut Cochin, Inserm, U567, 27 rue du faubourg St Jacques, 75014, Paris, France,

  2. L -C Bui and C Tomkiewicz: These authors contributed equally to this work.

Authors and Affiliations

  1. INSERM UMR-S 747, Paris, France

    L -C Bui, C Tomkiewicz, A Chevallier, S Pierre, A -S Bats, S Mota, M Garlatti, R Barouki & X Coumoul

  2. Université Paris Descartes, Centre Universitaire des Saints-Pères, Paris, France

    L -C Bui, C Tomkiewicz, A Chevallier, S Pierre, A -S Bats, S Mota, M Diry, C Transy, M Garlatti, R Barouki & X Coumoul

  3. INSERM U461, Faculté de Pharmacie, Chatenay-Malabry, France

    J Raingeaud & J Pierre

  4. INSERM U490, Paris, France

    M Diry & C Transy

  5. APHP, Hôpital Necker Enfants Malades, Paris, France

    R Barouki

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Correspondence to R Barouki or X Coumoul.

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

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Bui, LC., Tomkiewicz, C., Chevallier, A. et al. Nedd9/Hef1/Cas-L mediates the effects of environmental pollutants on cell migration and plasticity. Oncogene 28, 3642–3651 (2009). https://doi.org/10.1038/onc.2009.224

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  • DOI: https://doi.org/10.1038/onc.2009.224

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