Buchanan Paul J, McCloskey Karen D
Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland, BT9 7AE, UK.
National Institute of Cellular Biotechnology, School of Nursing and Human Science, Dublin City University, Glasnevin, Dublin 9, Ireland.
Eur Biophys J. 2016 Oct;45(7):621-633. doi: 10.1007/s00249-016-1144-z. Epub 2016 Jun 24.
The importance of ion channels in the hallmarks of many cancers is increasingly recognised. This article reviews current knowledge of the expression of members of the voltage-gated calcium channel family (Ca) in cancer at the gene and protein level and discusses their potential functional roles. The ten members of the Ca channel family are classified according to expression of their pore-forming α-subunit; moreover, co-expression of accessory α2δ, β and γ confers a spectrum of biophysical characteristics including voltage dependence of activation and inactivation, current amplitude and activation/inactivation kinetics. Ca channels have traditionally been studied in excitable cells including neurones, smooth muscle, skeletal muscle and cardiac cells, and drugs targeting the channels are used in the treatment of hypertension and epilepsy. There is emerging evidence that several Ca channels are differentially expressed in cancer cells compared to their normal counterparts. Interestingly, a number of Ca channels also have non-canonical functions and are involved in transcriptional regulation of the expression of other proteins including potassium channels. Pharmacological studies show that Ca canonical function contributes to the fundamental biology of proliferation, cell-cycle progression and apoptosis. This raises the intriguing possibility that calcium channel blockers, approved for the treatment of other conditions, could be repurposed to treat particular cancers. Further research will reveal the full extent of both the canonical and non-canonical functions of Ca channels in cancer and whether calcium channel blockers are beneficial in cancer treatment.
离子通道在多种癌症特征中的重要性日益受到认可。本文综述了电压门控钙通道家族（Ca）成员在癌症中基因和蛋白质水平表达的现有知识，并讨论了它们潜在的功能作用。Ca通道家族的十个成员根据其形成孔道的α亚基的表达进行分类；此外，辅助性α2δ、β和γ亚基的共表达赋予了一系列生物物理特性，包括激活和失活的电压依赖性、电流幅度以及激活/失活动力学。传统上，Ca通道是在可兴奋细胞中进行研究的，包括神经元、平滑肌、骨骼肌和心肌细胞，针对这些通道的药物用于治疗高血压和癫痫。有新证据表明，与正常细胞相比，几种Ca通道在癌细胞中存在差异表达。有趣的是，一些Ca通道还具有非经典功能，并参与包括钾通道在内的其他蛋白质表达的转录调控。药理学研究表明，Ca通道的经典功能有助于细胞增殖、细胞周期进展和凋亡等基本生物学过程。这就引发了一个有趣的可能性，即已被批准用于治疗其他病症的钙通道阻滞剂可以重新用于治疗特定癌症。进一步的研究将揭示Ca通道在癌症中经典和非经典功能的全貌，以及钙通道阻滞剂在癌症治疗中是否有益。
