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NaV1.5 enhances breast cancer cell invasiveness by increasing NHE1-dependent H+ efflux in caveolae

Oncogene volume 30, pages 2070–2076 (2011)Cite this article

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Abstract

NaV1.5 sodium channels enhance the invasiveness of breast cancer cells through the acidic-dependent activation of cysteine cathepsins. Here, we showed that the Na+/H+ exchanger type 1 (NHE1) was an important regulator of H+ efflux in breast cancer cells MDA-MB-231 and that its activity was increased by NaV1.5. NaV1.5 and NHE1 were colocalized in membrane rafts containing caveolin-1. The inhibition of NaV1.5 or NHE1 induced a similar reduction in cell invasiveness and extracellular matrix degradation; no additive effect was observed when they were simultaneously inhibited. Our study suggests that NaV1.5 and NHE1 are functionally coupled and enhance the invasiveness of cancer cells by increasing H+ efflux.

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Acknowledgements

We thank Dr Lin-Hua Jiang (University of Leeds, UK) for comments about the manuscript. We are grateful to Dr Ming Lei (University of Manchester, UK) for the generous gift of the anti-NaV1.5 antibody. This work was supported by the ‘Ministère de la Recherche et des Technologies’ and the ‘Institut National de la Santé et de la Recherche Médicale’ (Inserm), the ‘Association CANCEN’ and a grant from the ‘Ligue Nationale Contre le Cancer’. Lucie Brisson and Ludovic Gillet were recipients of fellowships from the ‘Région Centre’.

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Author notes

  1. S Roger and J Gore: These authors contributed equally to this work.

Authors and Affiliations

  1. Inserm U921, Nutrition, Croissance et Cancer, Université François Rabelais, Faculté de Médecine, Tours, France

    L Brisson, L Gillet, P Besson, S Roger & J Gore

  2. Institute of systems and membrane biology, University of Leeds, Leeds, UK

    S Calaghan

  3. Inserm U637 Physiopathologie cardiovasculaire, Université Montpellier-2, Montpellier Cedex, France

    J-Y Le Guennec

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  1. L Brisson
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  2. L Gillet
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  3. S Calaghan
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  4. P Besson
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  5. J-Y Le Guennec
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  6. S Roger
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  7. J Gore
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Correspondence to S Roger.

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Brisson, L., Gillet, L., Calaghan, S. et al. NaV1.5 enhances breast cancer cell invasiveness by increasing NHE1-dependent H+ efflux in caveolae. Oncogene 30, 2070–2076 (2011). https://doi.org/10.1038/onc.2010.574

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