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Lithium suppresses motility and invasivity of v-src-transformed cells by glutathione-dependent activation of phosphotyrosine phosphatases

Oncogene volume 28, pages 3246–3260 (2009)Cite this article

Abstract

Lithium has long been used for the treatment and prophylaxis of bipolar mood disorder. However, nerve cells are not the sole targets of lithium. Indeed, lithium was reported to target numerous cell types, and affect cell proliferation, differentiation and death. Thus, the idea has been raised that lithium may act on signaling pathways involved in neoplastic transformation. Indeed, the effect of lithium on tumor progression is currently being tested in a limited number of clinical trials. However, the molecular mechanisms by which lithium affects neoplastic transformation remain to be characterized. Here, using mouse fibroblasts transformed by the v-src oncogene as a model, we show that lithium drastically inhibits cell motility and compromises the invasive phenotype of v-src-transformed cells. In addition, we show that this effect is mediated by the activation of phosphotyrosine phosphatases, but not by the direct inhibition of the v-Src tyrosine kinase. Finally, we show that lithium activates phosphotyrosine phosphatases by the modulation of the redox status of the cell, independently of the Wnt and the inositol phosphate canonical pathways. Thus, this study supports the idea that lithium, acting similar to an antioxydizer, may have antimetastatic properties in vivo.

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Acknowledgements

We thank Pierre Jurdic and Philippe Gonzalo for helpfull discussions and critical reading of the paper. We acknowledge Aurélie Cornut for skillfull technical assistance. This work was supported by the Association pour la Recherche sur le Cancer (ARC), the Ligue Nationale contre le Cancer and the Région Rhône Alpes. BDN is a recipient of fellowships from the Ministère de la Recherche and the ARC.

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  1. B D Néel

    Present address: 4Current address: CEA/DSV/iBEB/SBTN Bât170, Laboratoire d’Etude des Protéines Cibles, BP 17171, 30 207 Bagnols sur Cèze Cedex, France,

Authors and Affiliations

  1. Université de Lyon, Institut de Biologie et Chimie des Protéines UMR 5086 CNRS-Université Lyon I, IFR 128, 7, Lyon cedex 07, France

    B D Néel, J Lopez & G Gillet

  2. Laboratoire de Biologie Moléculaire de la Cellule, Université de Lyon, UMR 5239 CNRS-Ecole normale supérieure de Lyon, IFR 128, Lyon cedex 07, France

    A Chabadel

  3. Hospices civils de Lyon, Fédération de Biochimie Nord, Hôpital de la Croix Rousse, 103, Grande rue de la Croix Rousse, Lyon cedex 04, France

    J Lopez

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Correspondence to G Gillet.

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

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Néel, B., Lopez, J., Chabadel, A. et al. Lithium suppresses motility and invasivity of v-src-transformed cells by glutathione-dependent activation of phosphotyrosine phosphatases. Oncogene 28, 3246–3260 (2009). https://doi.org/10.1038/onc.2009.190

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