How do voltage-gated sodium channels enhance migration and invasiveness in cancer cells?

• Voltage-gated sodium channels (VGSC) enhance cancer cell motility and invasiveness.
• A lot is known on how the activity, expression, degradation of VGSC are regulated.
• How VGSC enhance motility and invasiveness is poorly described and understood.
• Several proteins which are regulated by VGSC activity are known.
• Links are missing between VGSC, Na+ and these proteins.

Voltage-gated sodium channels are abnormally expressed in tumors, often as neonatal isoforms, while they are not expressed, or only at a low level, in the matching normal tissue. The level of their expression and their activity is related to the aggressiveness of the disease and to the formation of metastases. A vast knowledge on the regulation of their expression and functioning has been accumulated in normal excitable cells. This helped understand their regulation in cancer cells. However, how voltage-gated sodium channels impose a pro-metastatic behavior to cancer cells is much less documented. This aspect will be addressed in the review. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers.

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