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Molecular Cancer
Published in: Molecular Cancer 1/2014

Open Access 01-12-2014 | Short communication

Ranolazine inhibits NaV1.5-mediated breast cancer cell invasiveness and lung colonization

Authors: Virginie Driffort, Ludovic Gillet, Emeline Bon, Séverine Marionneau-Lambot, Thibauld Oullier, Virginie Joulin, Christine Collin, Jean-Christophe Pagès, Marie-Lise Jourdan, Stéphan Chevalier, Philippe Bougnoux, Jean-Yves Le Guennec, Pierre Besson, Sébastien Roger

Published in: Molecular Cancer | Issue 1/2014

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Abstract

Background

NaV1.5 voltage-gated sodium channels are abnormally expressed in breast tumours and their expression level is associated with metastatic occurrence and patients’ death. In breast cancer cells, NaV1.5 activity promotes the proteolytic degradation of the extracellular matrix and enhances cell invasiveness.

Findings

In this study, we showed that the extinction of NaV1.5 expression in human breast cancer cells almost completely abrogated lung colonisation in immunodepressed mice (NMRI nude). Furthermore, we demonstrated that ranolazine (50 μM) inhibited NaV1.5 currents in breast cancer cells and reduced NaV1.5-related cancer cell invasiveness in vitro. In vivo, the injection of ranolazine (50 mg/kg/day) significantly reduced lung colonisation by NaV1.5-expressing human breast cancer cells.

Conclusions

Taken together, our results demonstrate the importance of NaV1.5 in the metastatic colonisation of organs by breast cancer cells and indicate that small molecules interfering with NaV activity, such as ranolazine, may represent powerful pharmacological tools to inhibit metastatic development and improve cancer treatments.
Appendix
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Metadata
Title
Ranolazine inhibits NaV1.5-mediated breast cancer cell invasiveness and lung colonization
Authors
Virginie Driffort
Ludovic Gillet
Emeline Bon
Séverine Marionneau-Lambot
Thibauld Oullier
Virginie Joulin
Christine Collin
Jean-Christophe Pagès
Marie-Lise Jourdan
Stéphan Chevalier
Philippe Bougnoux
Jean-Yves Le Guennec
Pierre Besson
Sébastien Roger
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2014
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-13-264

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