Voltage-gated sodium channels and metastatic disease

Voltage-gated Na+ channels (VGSCs) are macromolecular protein complexes containing a pore-forming alpha subunit and smaller non-pore-forming beta subunits. VGSCs are expressed in metastatic cells from a number of cancers. In these cells, Na+ current carried by a subunits enhances migration, invasion and metastasis in vivo. In contrast, the beta 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 Na(v)1.5 alpha 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.