Voltage-gated sodium channels (VGSCs), which are abnormally expressed in various types of cancers such as breast cancer, prostate cancer, lung cancer, and cervical cancer, are involved in the metastatic process of invasion and migration. Nav1.5 is a poreforming a subunit of VGSC encoded by SCN5A. Various studies have demonstrated that Nav1.5, often as its neonatal splice form, is highly expressed in metastatic breast cancer cells. Abnormal activation and expression of Nav1.5 trigger a variety of cellular mechanisms, including changing H + efflux, promoting epithelial-to-mesenchymal transition (EMT) and the expression of cysteine cathepsin, to potentiate the metastasis and invasiveness of breast cancer cells in vitro and in vivo. Here, we systematically review the latest available data on the pro-metastatic effect of Nav1.5 and its underlying mechanisms in breast cancer. We summarize the factors affecting Nav1.5 expression in breast cancer cells, and discuss the potential of Nav1.5 blockers serving as candidates for breast cancer treatment.
Spider venoms are known to contain proteins and polypeptides that perform various
functions including antimicrobial, neurotoxic, analgesic, cytotoxic, necrotic,
and hemagglutinic activities. Currently, several classes of natural molecules
from spider venoms are potential sources of chemotherapeutics against tumor
cells. Some of the spider peptide toxins produce lethal effects on tumor cells
by regulating the cell cycle, activating caspase pathway or inactivating
mitochondria. Some of them also target the various types of ion channels
(including voltage-gated calcium channels, voltage-gated sodium channels, and
acid-sensing ion channels) among other pain-related targets. Herein we review
the structure and pharmacology of spider-venom peptides that are being used as
leads for the development of therapeutics against the pathophysiological
conditions including cancer and pain.
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