No data are currently available on the functional role of small conductance Ca2+‐activated K+ channels (SKCa) in ovarian cancer. Here, we characterized the role of SK2 (KCa2.2) in ovarian cancer cell migration and chemosensitivity. Using the selective non‐cell‐permeant SK2 inhibitor Lei‐Dab7, we identified functional SK2 channels at the plasma membrane, regulating store‐operated Ca2+ entry (SOCE) in both cell lines tested (COV504 and OVCAR3). Silencing KCNN2 with short interfering RNA (siRNA), or blocking SK2 activity with Lei‐Dab7, decreased cell migration. The more robust effect of KCNN2 knockdown compared to Lei‐Dab7 treatment suggested the involvement of functional intracellular SK2 channels in both cell lines. In cells treated with lysophosphatidic acid (LPA), an ovarian cancer biomarker of progression, SK2 channels are a key player of LPA pro‐migratory activity but their role in SOCE is abolished. Concerning chemotherapy, SK2 inhibition increased chemoresistance to Taxol® and low KCNN2 mRNA expression was associated with the worst prognosis for progression‐free survival in patients with serous ovarian cancer. The dual roles of SK2 mean that SK2 activators could be used as an adjuvant chemotherapy to potentiate treatment efficacy and SK2 inhibitors could be administrated as monotherapy to limit cancer cell dissemination.

中文翻译：

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质膜SK2通道活性调节高级别浆液性卵巢癌细胞的迁移和化疗敏感性

目前还没有关于小电导 Ca 的功能作用的数据2+‐活化钾+卵巢癌中的通道（SKCa）。在这里，我们描述了 SK2 (KCa2.2) 在卵巢癌细胞迁移和化疗敏感性中的作用。使用选择性非细胞渗透性 SK2 抑制剂 Lei-Dab7，我们确定了质膜上的功能性 SK2 通道，调节钙池操纵的 Ca2+在两个测试的细胞系（COV504 和 OVCAR3）中进入（SOCE）。沉默KCNN2使用短干扰 RNA (siRNA) 或使用 Lei-Dab7 阻断 SK2 活性，可减少细胞迁移。更稳健的效果KCNN2与 Lei-Dab7 治疗相比，敲低表明两种细胞系中都涉及功能性细胞内 SK2 通道。在用溶血磷脂酸（LPA）（一种卵巢癌进展生物标志物）处理的细胞中，SK2通道是LPA促迁移活性的关键参与者，但它们在SOCE中的作用被废除。关于化疗，SK2 抑制增加了对紫杉醇®的化疗耐药性并降低了KCNN2mRNA 表达与浆液性卵巢癌患者无进展生存的最差预后相关。SK2的双重作用意味着SK2激活剂可以用作辅助化疗以增强治疗效果，而SK2抑制剂可以作为单一疗法来限制癌细胞扩散。