KCa3.1 Channels and Glioblastoma: In Vitro Studies.
KCa3.1 Channels and Glioblastoma: In Vitro Studies.
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DOI：
10.2174/1570159x15666170808115821
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发表时间：
2018
影响因子：
5.3
通讯作者：
Huber SM
中科院分区：
文献类型：
--
作者：
Klumpp L;Sezgin EC;Skardelly M;Eckert F;Huber SM
包括脑肿瘤在内的几种肿瘤实体异常过表达中电导Ca 2+激活的KCa 3.1 K+通道。这些通道对肿瘤细胞的转化表型有显著贡献。检索了PubMed，以总结我们目前对肿瘤细胞（特别是胶质母细胞瘤细胞）中KCa 3.1通道活性的分子信号上游和下游以及效应子功能的了解。此外，KCa3.1的表达和功能的DNA双链断裂的修复实验确定在原代胶质母细胞瘤文化的丰富的前神经和间充质干细胞标志物的依赖。细胞质膜和线粒体内膜上的KCa 3.1通道通过调节细胞膜电位、细胞体积、Ca 2+信号和呼吸链等，对肿瘤细胞的迁移和侵袭、转移、细胞周期进程、氧耗和代谢、DNA损伤反应和细胞死亡等细胞过程具有重要的调控作用。此外，KCa3.1通道已被证明对抵抗放射治疗至关重要。因此，关于胶质母细胞瘤干细胞亚型中KCa3.1通道表达的原始体外数据提出KCa3.1作为癌症干细胞的间充质亚群的标志物，并表明KCa3.1有助于间充质胶质母细胞瘤干细胞的治疗抗性。这些数据表明，KCa3.1通道靶向与放射治疗相结合是根除耐药间充质胶质母细胞瘤干细胞的有前途的新工具。
Several tumor entities including brain tumors aberrantly overexpress intermediate conductance Ca2+ activated KCa3.1 K+ channels. These channels contribute significantly to the transformed phenotype of the tumor cells. PubMed was searched in order to summarize our current knowledge on the molecular signaling upstream and downstream and the effector functions of KCa3.1 channel activity in tumor cells in general and in glioblastoma cells in particular. In addition, KCa3.1 expression and function for repair of DNA double strand breaks was determined experimentally in primary glioblastoma cultures in dependence on the abundance of proneural and mesenchymal stem cell markers. By modulating membrane potential, cell volume, Ca2+ signals and the respiratory chain, KCa3.1 channels in both, plasma and inner mitochondrial membrane, have been demonstrated to regulate many cellular processes such as migration and tissue invasion, metastasis, cell cycle progression, oxygen consumption and metabolism, DNA damage response and cell death of cancer cells. Moreover, KCa3.1 channels have been shown to crucially contribute to resistance against radiotherapy. Futhermore, the original in vitro data on KCa3.1 channel expression in subtypes of glioblastoma stem(-like) cells propose KCa3.1 as marker for the mesenchymal subgroup of cancer stem cells and suggest that KCa3.1 contributes to the therapy resistance of mesenchymal glioblastoma stem cells. The data suggest KCa3.1 channel targeting in combination with radiotherapy as promising new tool to eradicate therapy-resistant mesenchymal glioblastoma stem cells.