Journal
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
Volume 369, Issue 1638, Pages -Publisher
ROYAL SOC
DOI: 10.1098/rstb.2013.0105
Keywords
voltage-gated sodium channel; metastasis; activity-dependent regulation; growth factor; hormone
Categories
Funding
- Pro Cancer Research Fund (PCRF)
- Medical Research Council [G1000508 (95657)]
- Cancer Research UK [12011] Funding Source: researchfish
- Medical Research Council [G1000508] Funding Source: researchfish
- MRC [G1000508] Funding Source: UKRI
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Although ion channels are increasingly being discovered in cancer cells in vitro and in vivo, and shown to contribute to different aspects and stages of the cancer process, much less is known about the mechanisms controlling their expression. Here, we focus on voltage-gated Na+ channels (VGSCs) which are upregulated in many types of carcinomas where their activity potentiates cell behaviours integral to the metastatic cascade. Regulation of VGSCs occurs at a hierarchy of levels from transcription to post-translation. Importantly, mainstream cancer mechanisms, especially hormones and growth factors, play a significant role in the regulation. On the whole, in major hormone-sensitive cancers, such as breast and prostate cancer, there is a negative association between genomic steroid hormone sensitivity and functional VGSC expression. Activity-dependent regulation by positive feedback has been demonstrated in strongly metastatic cells whereby the VGSC is self-sustaining, with its activity promoting further functional channel expression. Such auto-regulation is unlike normal cells in which activity-dependent regulation occurs mostly via negative feedback. Throughout, we highlight the possible clinical implications of functional VGSC expression and regulation in cancer.
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