Molecular pharmacology of voltage-gated sodium channel expression in metastatic disease: clinical potential of neonatal Nav1.5 in breast cancer

摘要: A variety of ion channels have been detected in cancer cells. In particular, upregulation voltage-gated sodium (VGSCs) has associated pathophysiologically with several strongly metastatic carcinomas. This review emphasises breast cancer. Inhibiting VGSC activity a number independent ways, using the highly selective tetrodotoxin (TTX), gene silencing and blocking polyclonal antibody, suppressed range cellular behaviors, especially directional motility invasion, integral to cascade. Conversely, transfecting into weakly invasive human prostate cell line significantly increased invasiveness. vivo, also, expression correlated positively status. It suggested, therefore (i) that is an early event progression (ii) 'switch,' necessary sufficient for engaging cells state. Importantly, where studied, mainly cancers, dominant (Nav1.7 Nav1.5, respectively) was found be embryonic/neonatal splice variant, consistent being "oncofoetal." cancer, molecular difference between adult neonatal isoforms VGSC/Nav1.5 largest (31 base pairs, generating 7 amino acid differences). We propose Nav1.5 novel marker significant clinical potential management describe approaches which may enable tumour-specific targeting. These include various small-molecule drugs, small-interfering RNA, monoclonal antibody natural neurotoxins.