Inserm, U921, F-37032 Tours, France.
Exp Cell Res. 2009 Dec 10;315(20):3620-30. doi: 10.1016/j.yexcr.2009.07.021. Epub 2009 Jul 30.
Cell migration and invasion are required for tumour cells to spread from the primary tumour bed so as to form secondary tumours at distant sites. We report evidence of an unusual expression of KCa2.3 (SK3) protein in melanoma cell lines but not in normal melanocytes. Knockdown of the KCa2.3 channel led to plasma membrane depolarization, decreased 2D and 3D cell motility. Conversely, enforced production of KCa2.3 protein in KCa2.3 non-expressing cells led to the plasma membrane becoming hyperpolarized, and enhanced cell motility. In contrast, KCa3.1 channels had no effect on cell motility despite an active role in regulating membrane potential. Our data also suggest that membrane hyperpolarization increases melanoma cell motility and that this occurs through the KCa2.3 channel. Our findings reveal a previously unknown function of the KCa2.3 channel, and suggest that the KCa2.3 channel might be the only member of the Ca(2+)-activated K(+) channel family involved in melanoma cell motility pathways.
肿瘤细胞需要迁移和侵袭，才能从原发性肿瘤床扩散，从而在远处形成继发性肿瘤。我们报告了一种异常表达 KCa2.3（SK3）蛋白的证据，这种蛋白存在于黑色素瘤细胞系中，但不存在于正常黑素细胞中。敲低 KCa2.3 通道导致质膜去极化，降低了 2D 和 3D 细胞迁移。相反，在不表达 KCa2.3 蛋白的细胞中强制表达 KCa2.3 蛋白，导致质膜超极化，并增强细胞迁移。相比之下，KCa3.1 通道尽管在调节膜电位方面发挥着积极作用，但对细胞迁移没有影响。我们的数据还表明，质膜超极化增加了黑色素瘤细胞的迁移能力，而这是通过 KCa2.3 通道实现的。我们的研究结果揭示了 KCa2.3 通道以前未知的功能，并表明 KCa2.3 通道可能是唯一参与黑色素瘤细胞迁移途径的钙激活钾通道家族成员。
