Voltage gated sodium channels in cancer and their potential mechanisms of action.

IF 3.3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Channels Pub Date : 2019-12-01 DOI:10.1080/19336950.2019.1666455

Madeline Angus, Peter Ruben

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Abstract

Voltage gated sodium channels (VGSC) are implicated in cancer cell invasion and metastasis. However, the mechanism by which VGSC increase cell invasiveness and probability of metastasis is still unknown. In this review we outline lesser known functions of VGSC outside of action potential propagation, and the current understanding of the effects of VGSC in cancer. Finally, we discuss possible downstream effects of VGSC activation in cancer cells. After extensive review of the literature, the most likely role of VGSC in cancer is in the invadopodia, the leading edge of metastatic cancer cells. Sodium gradients are used to drive many biological processes in the body, and invadopodia may be similar. The function of the sodium hydrogen exchanger (NHE) and sodium calcium exchanger (NCX) are driven by sodium gradients. Voltage gated calcium channels, activated by membrane depolarization, are also capable of becoming activated in response to VGSC activity. Changes to hydrogen ion exchange or calcium handling have functional consequences for invadopodia and would explain the relationship between VGSC expression and invasiveness of cancer cells.

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癌症中的电压门控钠通道及其潜在作用机制。

电压门控钠通道（VGSC）与癌细胞的侵袭和转移有关。然而，VGSC 增加细胞侵袭性和转移几率的机制仍不清楚。在这篇综述中，我们概述了 VGSC 在动作电位传播之外鲜为人知的功能，以及目前对 VGSC 在癌症中的作用的理解。最后，我们讨论了癌细胞中 VGSC 激活可能产生的下游效应。在广泛查阅文献后，VGSC 在癌症中最有可能发挥的作用是在转移癌细胞的前沿--侵袭体中。体内的许多生物过程都是由钠梯度驱动的，内生癌细胞也可能与此类似。钠氢交换器（NHE）和钠钙交换器（NCX）的功能由钠梯度驱动。由膜去极化激活的电压门控钙通道也能在 VGSC 活动时被激活。氢离子交换或钙处理的变化会对侵袭性细胞产生功能性影响，并能解释 VGSC 表达与癌细胞侵袭性之间的关系。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Channels 生物-生化与分子生物学

CiteScore

5.90

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Channels is an open access journal for all aspects of ion channel research. The journal publishes high quality papers that shed new light on ion channel and ion transporter/exchanger function, structure, biophysics, pharmacology, and regulation in health and disease. Channels welcomes interdisciplinary approaches that address ion channel physiology in areas such as neuroscience, cardiovascular sciences, cancer research, endocrinology, and gastroenterology. Our aim is to foster communication among the ion channel and transporter communities and facilitate the advancement of the field.