Abstract
Nav1.5 is one of the nine voltage-gated sodium channel-alpha subunit (VGSC-α) family members. The Nav1.5 channel typically carries an inward sodium ion current that depolarises the membrane potential during the upstroke of the cardiac action potential. The neonatal isoform of Nav1.5, nNav1.5, is produced via VGSC-α alternative splicing. nNav1.5 is known to potentiate breast cancer metastasis. Despite their well-known biological functions, the immunological perspectives of these channels are poorly explored. The current review has attempted to summarise the triad between Nav1.5 (nNav1.5), breast cancer, and the immune system. To date, there is no such review available that encompasses these three components as most reviews focus on the molecular and pharmacological prospects of Nav1.5. This review is divided into three major subsections: (1) the review highlights the roles of Nav1.5 and nNav1.5 in potentiating the progression of breast cancer, (2) focuses on the general connection between breast cancer and the immune system, and finally (3) the review emphasises the involvements of Nav1.5 and nNav1.5 in the functionality of the immune system and the immunogenicity. Compared to the other subsections, section three is pretty unexploited; it would be interesting to study this subsection as it completes the triad.
Highlights
Nav1.5 is one of the nine members of the VGSC family.VGSCs are heteromeric membrane protein complexes
Aside from that, Chioni et al [64] added that the Na+ current conducted by Nav1.5 activates the phosphorylation of protein kinase A (PKA), which increases the expression of Nav1.5 at the transcriptional level, but does not cause an increase in the total protein level
It has previously been suggested that the employment of treatment such as chemotherapy and radiation in breast cancer may stimulate the expression of MHC class I [167]. Such phenomenon is supported via findings discovered by Murthadha et al [168], where the downregulation of nNav1.5 in aggressive breast cancer cells positively upregulates the expression of MHC class I
Summary
Nav1.5 (encoded by the SCN5A gene) is one of the nine members of the VGSC family. VGSCs are heteromeric membrane protein complexes. In terms of conformational change, VGSC transits between three distinct conformational states whenever there is a change in the membrane potential (depolarisation) These unique conformational figures are known as resting (closed), activated (open), and inactivated (closed) states [5]. Aside from charge reversal and amino acid substitutions, there is one other feature that distinguishes Nav1.5 from nNav1.5 This feature is known as the ability to resist the suppressive effects of acidification. The available review papers only focus on the metastatic capacity of Nav1.5 and nNav1.5 in potentiating breast cancer metastasis [22] and the pharmacological aspects of these sodium channels [23]. The Roles of Nav1.5 and nNav1.5 in Potentiating the Progression of Breast Cancer
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