title: Voltage-gated sodium channels and metastatic disease.
abstract: Voltage-gated Na (+)  channels (VGSCs) are macromolecular protein complexes containing a pore-forming α subunit and smaller non-pore-forming β subunits. VGSCs are expressed in metastatic cells from a number of cancers. In these cells, Na (+)  current carried by α subunits enhances migration, invasion and metastasis in vivo. In contrast, the β subunits mediate cellular adhesion and process extension. The prevailing hypothesis is that VGSCs are upregulated in cancer, in general favoring an invasive/metastatic phenotype, although the mechanisms are still not fully clear. Expression of the Nav 1.5 α subunit associates with poor prognosis in clinical breast cancer specimens, suggesting that VGSCs may have utility as prognostic markers for cancer progression. Furthermore, repurposing existing VGSC-blocking therapeutic drugs may provide a new strategy to improve outcomes in patients suffering from metastatic disease, which is the major cause of cancer-related deaths, and for which there is currently no cure.
authors.affiliation: Department of Biology, University of York, York, UK. william.brackenbury@york.ac.uk
authors.forename: William J
authors.initials: WJ
authors.lastname: Brackenbury
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D027682:Cation Transport Proteins / Q000378:metabolism; D051242:Caveolin 1 / Q000378:metabolism; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System; D009362:Neoplasm Metastasis; D012964:Sodium / Q000378:metabolism; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism*
chemical_list: D027682:Cation Transport Proteins; D051242:Caveolin 1; C490998:SLC9A1 protein, human; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D061566:Voltage-Gated Sodium Channels; D012964:Sodium; D002118:Calcium