Voltage-gated sodium channels: from roles and mechanisms in the metastatic cell behavior to clinical potential as therapeutic targets.

Front Pharmacol

Departamento de Neuropatología Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico.

Published: June 2023

AI Article Synopsis

  • VGSCs, known for their role in generating action potentials in excitable cells, have recently been found to have non-canonical functions linked to cancer progression and metastasis.
  • Dysregulation of VGSC expression and activity is associated with aggressive cancer features, positioning them as potential markers and prognostic factors for cancer.
  • Current research focuses on understanding the roles of VGSC subunits in metastatic processes and exploring the use of FDA-approved drugs and new compounds to inhibit VGSCs, aiming to reduce cancer cell invasion and improve treatment strategies.

Article Abstract

During the second half of the last century, the prevalent knowledge recognized the voltage-gated sodium channels (VGSCs) as the proteins responsible for the generation and propagation of action potentials in excitable cells. However, over the last 25 years, new non-canonical roles of VGSCs in cancer hallmarks have been uncovered. Their dysregulated expression and activity have been associated with aggressive features and cancer progression towards metastatic stages, suggesting the potential use of VGSCs as cancer markers and prognostic factors. Recent work has elicited essential information about the signalling pathways modulated by these channels: coupling membrane activity to transcriptional regulation pathways, intracellular and extracellular pH regulation, invadopodia maturation, and proteolytic activity. In a promising scenario, the inhibition of VGSCs with FDA-approved drugs as well as with new synthetic compounds, reduces cancer cell invasion and cancer progression . The purpose of this review is to present an update regarding recent advances and ongoing efforts to have a better understanding of molecular and cellular mechanisms on the involvement of both pore-forming α and auxiliary β subunits of VGSCs in the metastatic processes, with the aim at proposing VGSCs as new oncological markers and targets for anticancer treatments.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10348687PMC
http://dx.doi.org/10.3389/fphar.2023.1206136DOI Listing

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