Voltage-gated sodium channels and metastatic disease

TY - JOUR

T1 - Voltage-gated sodium channels and metastatic disease

AU - Brackenbury, William J

N1 - © 2012 Landes Bioscience. This is an author produced version of a paper published in Channels . Uploaded in accordance with the publisher's self-archiving policy.

PY - 2012/9

Y1 - 2012/9

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84868150677&partnerID=8YFLogxK

U2 - 10.4161/chan.21910

DO - 10.4161/chan.21910

M3 - Literature review

C2 - 22992466

SN - 1933-6950

VL - 6

SP - 352

EP - 361

JO - Channels (Austin)

JF - Channels (Austin)

IS - 5

ER -