Ca(V) channels and cancer: canonical functions indicate benefits of repurposed drugs as cancer therapeutics.
Ca(V) channels and cancer: canonical functions indicate benefits of repurposed drugs as cancer therapeutics.
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DOI：
10.1007/s00249-016-1144-z
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发表时间：
2016-10
影响因子：
2
通讯作者：
McCloskey, Karen D.
中科院分区：
文献类型：
--
作者：
Buchanan, Paul J.;McCloskey, Karen D.
离子通道在许多癌症标志中的重要性越来越被认识到。本文综述了目前的知识表达的电压门控钙通道家族（CaV）的成员在癌症中的基因和蛋白质水平，并讨论其潜在的功能作用。CaV通道家族的10个成员根据其成孔α亚基的表达进行分类;此外，辅助α2δ、β和γ的共表达赋予了一系列生物物理特征，包括激活和失活的电压依赖性、电流幅度和激活/失活动力学。传统上，CaV通道在包括神经元、平滑肌、骨骼肌和心脏细胞在内的可兴奋细胞中进行研究，针对这些通道的药物用于治疗高血压和癫痫。有新的证据表明，几种CaV通道在癌细胞中的表达与正常细胞相比存在差异。有趣的是，许多CaV通道也具有非经典功能，并参与其他蛋白质（包括钾通道）表达的转录调控。药理学研究表明，CaV的典型功能有助于增殖，细胞周期进程和凋亡的基础生物学。这提出了一种有趣的可能性，即钙通道阻滞剂，批准用于治疗其他疾病，可以重新用于治疗特定的癌症。进一步的研究将揭示CaV通道在癌症中的典型和非典型功能的全部范围，以及钙通道阻滞剂是否有益于癌症治疗。
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 (CaV) in cancer at the gene and protein level and discusses their potential functional roles. The ten members of the CaV 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. CaV 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 CaV channels are differentially expressed in cancer cells compared to their normal counterparts. Interestingly, a number of CaV 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 CaV 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 CaV channels in cancer and whether calcium channel blockers are beneficial in cancer treatment.
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影响因子：
3.8
作者：
Devore, Elizabeth E.;Kim, Sung;Ramin, Cody A.;Wegrzyn, Lani R.;Massa, Jennifer;Holmes, Michelle D.;Michels, Karin B.;Tamimi, Rulla M.;Forman, John P.;Schernhammer, Eva S.
通讯作者：
Schernhammer, Eva S.
影响因子：
5.7
作者：
Davis, Sally J.;Sheppard, Karen E.;Gorringe, Kylie L.
通讯作者：
Gorringe, Kylie L.
影响因子：
2.6
作者：
Chen, Qi;Zhang, Qianwen;He, Jia
通讯作者：
He, Jia
影响因子：
2.9
作者：
Emerick, Mark C.;Stein, Rebecca;Agnew, William S.
通讯作者：
Agnew, William S.
影响因子：
6.4
作者：
Boormans, Joost L.;Korsten, Hanneke;Trapman, Jan
通讯作者：
Trapman, Jan