title: Na(V)1.5 enhances breast cancer cell invasiveness by increasing NHE1-dependent H(+) efflux in caveolae.
abstract: Na(V)1.5 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 Na(V)1.5. Na(V)1.5 and NHE1 were colocalized in membrane rafts containing caveolin-1. The inhibition of Na(V)1.5 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 Na(V)1.5 and NHE1 are functionally coupled and enhance the invasiveness of cancer cells by increasing H(+) efflux.
authors.affiliation: Inserm U921, Nutrition, Croissance et Cancer, Université François Rabelais, Faculté de Médecine, Tours, France.
authors.forename: L
authors.initials: L
authors.lastname: Brisson
authors.forename: L
authors.initials: L
authors.lastname: Gillet
authors.forename: S
authors.initials: S
authors.lastname: Calaghan
authors.forename: P
authors.initials: P
authors.lastname: Besson
authors.forename: J-Y
authors.initials: JY
authors.lastname: Le Guennec
authors.forename: S
authors.initials: S
authors.lastname: Roger
authors.forename: J
authors.initials: J
authors.lastname: Gore
mesh_terms: D001692:Biological Transport; D001943:Breast Neoplasms / Q000473:pathology*; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D021941:Caveolae / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D006863:Hydrogen-Ion Concentration; D042541:Intracellular Space / Q000737:chemistry / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D062554:NAV1.5 Voltage-Gated Sodium Channel; D009361:Neoplasm Invasiveness; D021381:Protein Transport; D011522:Protons; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism*
chemical_list: D027682:Cation Transport Proteins; D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; D011522:Protons; C568320:SCN5A protein, human; C490998:SLC9A1 protein, human; D015222:Sodium Channels; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers