Department of Biology, August Krogh Building, Universitetsparken 13, 2100, Copenhagen Ø, Denmark.
Pflugers Arch. 2013 Dec;465(12):1753-62. doi: 10.1007/s00424-013-1315-z. Epub 2013 Jul 7.
Members of the TMEM16 family have recently been described as Ca(2+)-activated Cl(-) channels. They have been implicated in cancer and appear to be associated with poor patient prognosis. Here, we investigate the role of TMEM16 channels in cell migration, which is largely unknown. We focused on TMEM16A and TMEM16F channels that have the highest expression of TMEM16 channels in Ehrlich Lettre ascites (ELA) cells. Due to the lack of specific pharmacological modulators, we employed a miRNA approach and stably knocked down the expression of TMEM16A and TMEM16F channels, respectively. Migration analysis shows that TMEM16A KD clones are affected in their directional migration, whereas TMEM16F KD clones show a 40 % reduced rate of cell migration. Moreover, TMEM16A KD clones have a smaller projected cell area, and they are rounder than TMEM16F KD clones. The morphological changes are linearly correlated with the directionality of cells. TMEM16A and TMEM16F, thus, have an important function in cell migration-TMEM16A in directional migration, TMEM16F in determination of the speed of migration. We conclude that TMEM16A and TMEM16F channels have a distinct impact on the steering and motor mechanisms of migrating ELA cells.
TMEM16 家族的成员最近被描述为 Ca(2+)-激活的 Cl(-)通道。它们与癌症有关，似乎与患者预后不良有关。在这里，我们研究了 TMEM16 通道在细胞迁移中的作用，这在很大程度上是未知的。我们专注于 TMEM16A 和 TMEM16F 通道，它们在 Ehrlich Lettre 腹水 (ELA) 细胞中表达最高的 TMEM16 通道。由于缺乏特异性的药理学调节剂，我们采用了 miRNA 方法，分别稳定敲低 TMEM16A 和 TMEM16F 通道的表达。迁移分析表明，TMEM16A KD 克隆在其定向迁移中受到影响，而 TMEM16F KD 克隆的细胞迁移率降低了 40%。此外，TMEM16A KD 克隆的投影细胞面积较小，比 TMEM16F KD 克隆更圆。形态变化与细胞的方向性呈线性相关。因此，TMEM16A 和 TMEM16F 在细胞迁移中具有重要功能-TMEM16A 参与定向迁移，TMEM16F 参与迁移速度的确定。我们得出结论，TMEM16A 和 TMEM16F 通道对迁移 ELA 细胞的转向和运动机制有明显的影响。
