Dataset Information

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

ABSTRACT:

Background

Na(V)1.5 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, Na(V)1.5 activity promotes the proteolytic degradation of the extracellular matrix and enhances cell invasiveness.

Findings

In this study, we showed that the extinction of Na(V)1.5 expression in human breast cancer cells almost completely abrogated lung colonisation in immunodepressed mice (NMRI nude). Furthermore, we demonstrated that ranolazine (50 ?M) inhibited Na(V)1.5 currents in breast cancer cells and reduced Na(V)1.5-related cancer cell invasiveness in vitro. In vivo, the injection of ranolazine (50 mg/kg/day) significantly reduced lung colonisation by Na(V)1.5-expressing human breast cancer cells.

Conclusions

Taken together, our results demonstrate the importance of Na(V)1.5 in the metastatic colonisation of organs by breast cancer cells and indicate that small molecules interfering with Na(V) activity, such as ranolazine, may represent powerful pharmacological tools to inhibit metastatic development and improve cancer treatments.

SUBMITTER: Driffort V

PROVIDER: S-EPMC4295566 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Publications

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

Driffort Virginie V Gillet Ludovic L Bon Emeline E Marionneau-Lambot Séverine S Oullier Thibauld T Joulin Virginie V Collin Christine C Pagès Jean-Christophe JC Jourdan Marie-Lise ML Chevalier Stéphan S Bougnoux Philippe P Le Guennec Jean-Yves JY Besson Pierre P Roger Sébastien S

Molecular cancer 20141211

<h4>Background</h4>Na(V)1.5 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, Na(V)1.5 activity promotes the proteolytic degradation of the extracellular matrix and enhances cell invasiveness.<h4>Findings</h4>In this study, we showed that the extinction of Na(V)1.5 expression in human breast cancer cells almost completely abrogated lung colonisation in immunodep ...[more]

PMID: 25496128

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Dataset Information

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

Background

Findings

Conclusions

Publications

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

Similar Datasets

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