title: 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.
  
  
  RESULTS
  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 μM) 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.
authors.forename: Virginie
authors.initials: V
authors.lastname: Driffort
authors.forename: Ludovic
authors.initials: L
authors.lastname: Gillet
authors.forename: Emeline
authors.initials: E
authors.lastname: Bon
authors.forename: Séverine
authors.initials: S
authors.lastname: Marionneau-Lambot
authors.forename: Thibauld
authors.initials: T
authors.lastname: Oullier
authors.forename: Virginie
authors.initials: V
authors.lastname: Joulin
authors.forename: Christine
authors.initials: C
authors.lastname: Collin
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Pagès
authors.forename: Marie-Lise
authors.initials: ML
authors.lastname: Jourdan
authors.forename: Stéphan
authors.initials: S
authors.lastname: Chevalier
authors.forename: Philippe
authors.initials: P
authors.lastname: Bougnoux
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Le Guennec
authors.affiliation: Inserm UMR1069, Nutrition, Croissance et Cancer, Université François-Rabelais de Tours, 10 Boulevard Tonnellé, Tours 37032, France. pierre.besson@univ-tours.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Besson
authors.forename: Sébastien
authors.initials: S
authors.lastname: Roger
mesh_terms: D000083:Acetanilides / Q000494:pharmacology*; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D006801:Humans; D008168:Lung / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000473:pathology; D010879:Piperazines / Q000494:pharmacology*; D000069458:Ranolazine
chemical_list: D000083:Acetanilides; D062554:NAV1.5 Voltage-Gated Sodium Channel; D010879:Piperazines; C568320:SCN5A protein, human; D000069458:Ranolazine