Inserm, U921, Tours, F-37032 France.
Curr Med Chem. 2012;19(5):697-713. doi: 10.2174/092986712798992039.
Many studies have reported changes in potassium channel expression in many cancers and the involvement of these channels in various stages of cancer progression. By contrast, data concerning SKCa channels (small conductance calcium-activated potassium channels) have only recently become available. This review aims i) to present the structure and physiology of SKCa channels, ii) to provide an overview of published data concerning the SKCa proteins produced in tumor cells, and, whenever possible, the biological function assigned to them and iii) to review previous and novel modulators of SKCa channels. SKCa channels are activated by low concentrations of intracellular calcium and consist of homo- or heteromeric assemblies of α-subunits named SK1, SK2 and SK3. SK2-3 channels are expressed in tumors and have been assigned a biological function in cancer cells: the enhancement of cell proliferation and cell migration by hijacking the functions of SK2 and SK3 channels, respectively. Two major classes of SKCa modulators have been described: toxins (apamin) and small synthetic molecules. Most SKCa blockers are pore blockers, but some modify the calcium sensitivity of SKCa channels without interacting with the apamin binding site. In this review, we present edelfosine and ohmline as atypical anticancer agents and novel SK3 inhibitors. Edelfosine and ohmline are synthetic alkyl-lipids with structures different from all previously described SKCa modulators. They should pave the way for the development of a new class of migration-targeted anticancer agents. We believe that such blockers have potential for use in the prevention or treatment of metastasis.
许多研究报告指出，钾通道表达在许多癌症中发生改变，并且这些通道参与癌症进展的各个阶段。相比之下，有关 SKCa 通道（小电导钙激活钾通道）的数据最近才出现。这篇综述的目的是：i）介绍 SKCa 通道的结构和生理学，ii）提供有关肿瘤细胞产生的 SKCa 蛋白的已发表数据的概述，并且在可能的情况下，分配给它们的生物学功能，以及 iii）回顾 SKCa 通道的先前和新型调节剂。SKCa 通道被低浓度的细胞内钙激活，由称为 SK1、SK2 和 SK3 的 α-亚基组成同源或异源二聚体。SK2-3 通道在肿瘤中表达，并在癌细胞中赋予了生物学功能：通过分别劫持 SK2 和 SK3 通道的功能来增强细胞增殖和细胞迁移。已经描述了两种主要类型的 SKCa 调节剂：毒素（蜂毒肽）和小分子合成物。大多数 SKCa 阻断剂是孔阻滞剂，但有些则在不与蜂毒肽结合位点相互作用的情况下调节 SKCa 通道的钙敏感性。在这篇综述中，我们介绍了埃德尔福辛和 ohmline 作为非典型抗癌剂和新型 SK3 抑制剂。埃德尔福辛和 ohmline 是具有与所有先前描述的 SKCa 调节剂不同结构的合成烷基脂质。它们应为开发新型迁移靶向抗癌剂铺平道路。我们相信，这些阻断剂有可能用于预防或治疗转移。
