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NFAT3 transcription factor inhibits breast cancer cell motility by targeting the Lipocalin 2 gene

Oncogene volume 29, pages 2292–2301 (2010)Cite this article

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Abstract

NFAT1 and NFAT5 act as pro-invasive and pro-migratory transcription factors in breast carcinoma, contributing to the formation of metastases. We report that NFAT3 is specifically expressed in estrogen receptor α positive (ERA+) breast cancer cells. We show that NFAT3 inhibits by itself the invasion capacity of ERA+ breast cancer cells and needs to cooperate with ERA to inhibit their migration. Conversely, NFAT3 downregulation results in actin reorganization associated with increased migration and invasion capabilities. NFAT3 signaling reduces migration through inhibition of Lipocalin 2 (LCN2) gene expression. Collectively, our study unravels an earlier unknown NFAT3/LCN2 axis that critically controls motility in breast cancer.

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Acknowledgements

We thank H de Thé, D Auboeuf and members of their laboratories for insightful discussions. We thank E Turpin, P Bertheau for providing their microarray data. We thank J L Poyet for providing the T7-pcDNA3 vector and G lazennec for the ERα expression vector. We thank T Hoey for providing the human NFAT3 expression vector. We thank J-C Gluckman for reading the paper. We thank N Setterblad at the Service Commun d’Imagerie Cellulaire et Moléculaire of the Institut Universitaire d’Hématologie IFR105 for confocal microscopy. The Service Commun d’Imagerie Cellulaire et Moléculaire is supported by grants from the Conseil Régional d’Ile-de-France and the Ministère de la Recherche. M Fougère was supported by a doctoral grant from INSERM Région Ile-de-France and an ARC fellowship. B Gaudineau was supported by a grant from the Cancéropole Ile-de-France and J Barbier by a grant from the Research Ministry. This work was supported by the INSERM AVENIR Program and grants from Ligue Nationale contre le Cancer, the Comité de Paris of Ligue Nationale contre le Cancer, ARC, and the Comité Tumeurs de la Fondation de France and the Cancéropole Ile-de-France.

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Authors and Affiliations

  1. CNRS UMR7212, INSERM U944, Université Paris Diderot, Institut d’Hématologie, Hôpital Saint-Louis, Paris, Cedex 10, France

    M Fougère, B Gaudineau, F Guaddachi, J-P Feugeas & S Jauliac

  2. INSERM U685/AVENIR, Centre Hayem, Institut d’Hématologie, Hôpital Saint-Louis, Paris, Cedex 10, France

    J Barbier & D Auboeuf

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  1. M Fougère
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Correspondence to S Jauliac.

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Fougère, M., Gaudineau, B., Barbier, J. et al. NFAT3 transcription factor inhibits breast cancer cell motility by targeting the Lipocalin 2 gene. Oncogene 29, 2292–2301 (2010). https://doi.org/10.1038/onc.2009.499

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