Electromagnetic fields alter the motility of metastatic breast cancer cells
Electromagnetic fields alter the motility of metastatic breast cancer cells
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DOI：
10.1038/s42003-019-0550-z
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发表时间：
2019-08-08
影响因子：
5.9
通讯作者：
Song, Jonathan W.
中科院分区：
文献类型：
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作者：
Garg, Ayush Arpit;Jones, Travis H.;Song, Jonathan W.
细胞与其环境之间的相互作用影响着关键的生理过程，如它们的迁移倾向。然而，由外部施加的电信号控制的定向迁移知之甚少。利用一种新型微流控平台，我们发现转移性乳腺癌细胞对弱（类似于100 μ V cm(-1)）、不对称、非接触的感应电场（ief）的净方向有感知和响应。ief抑制表皮生长因子受体（EGFR）的激活，阻止富含肌动蛋白的丝状足的形成，并阻碍egf处理的乳腺癌细胞的运动。干扰素的定向作用被Akt磷酸化抑制所抵消。此外，ief与Akt抑制剂联合使用使egf促进的运动性降低到低于未治疗对照组的水平。这些结果为分离细胞运动和干扰素之间的耦合机制迈出了一步，为干扰素如何靶向多种分化的癌细胞信号传导机制提供了有价值的见解，并证明了电信号是癌细胞迁移的基本调节因子。
Interactions between cells and their environment influence key physiologic processes such as their propensity to migrate. However, directed migration controlled by extrinsically applied electrical signals is poorly understood. Using a novel microfluidic platform, we found that metastatic breast cancer cells sense and respond to the net direction of weak (similar to 100 mu V cm(-1)), asymmetric, non-contact induced Electric Fields (iEFs). iEFs inhibited EGFR (Epidermal Growth Factor Receptor) activation, prevented formation of actin-rich filopodia, and hindered the motility of EGF-treated breast cancer cells. The directional effects of iEFs were nullified by inhibition of Akt phosphorylation. Moreover, iEFs in combination with Akt inhibitor reduced EGF-promoted motility below the level of untreated controls. These results represent a step towards isolating the coupling mechanism between cell motility and iEFs, provide valuable insights into how iEFs target multiple diverging cancer cell signaling mechanisms, and demonstrate that electrical signals are a fundamental regulator of cancer cell migration.