EGF enhances the migration of cancer cells by up-regulation of TRPM7

EGF enhances the migration of cancer cells by up-regulation of TRPM7
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EGF 通过上调 TRPM7 增强癌细胞的迁移。

DOI:
10.1016/j.ceca.2011.09.003
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发表时间:
2011-12-01
期刊:
影响因子:
4
通讯作者:
Zhang, Hailin
Zhang, Hailin
中科院分区:
生物学2区
文献类型:
--
作者:
Gao, Haixia;Chen, Xingjuan;Zhang, Hailin

文献摘要

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离子通道参与肿瘤细胞的迁移,这是肿瘤细胞侵袭和转移所必需的。在本文中,我们描述了瞬时受体电位M7(TRPM7)通道与表皮生长因子(EGF)在肺癌细胞迁移中的相互作用,表皮生长因子是癌症发展中的一个重要因素。首先通过电生理学、药理学和RNA干扰对A549细胞中的TRPM7电流进行了表征。去除细胞外溶液中的Ca²⁺不仅增强了一个大的内向电流,还消除了外向整流作用。200μM的2 - 氨基乙氧基二苯硼酸(2 - APB)抑制了外向和内向的TRPM7电流,同时恢复了外向整流特性。EGF极大地增强了A549细胞的迁移,还显著上调了TRPM7膜蛋白的表达以及TRPM7电流的幅度。通过RNA干扰或药物抑制TRPM7的功能,不仅逆转了EGF增强的A549细胞迁移,还抑制了在无EGF时A549细胞的基础迁移。因此,TRPM7似乎在EGF诱导的A549细胞迁移中起着关键作用,因此可能是肺癌的一个潜在治疗靶点。(C)2011爱思唯尔有限公司。保留所有权利。
Ion channels involved in the migration of tumor cells that is required for their invasion and metastasis. In this paper, we describe the interaction of TRPM7 channel and epidermal growth factor (EGF), an important player in cancer development in the migration of lung cancer cells. The TRPM7 currents in A549 cells were first characterized by means of electrophysiology, pharmacology and RNA interference. Removing Ca2+ from the extracellular solution not only potentiated a large inward current, but also abolished the outward rectification. 200 mu M 2-APB inhibited the outward and the inward TRPM7 currents and at the same time restored the property of outward rectification. EGF greatly enhanced the migration of A549 cells, and also markedly up-regulated the membrane protein expression of TRPM7 and the amplitude of TRPM7 currents. Depressing the function of TRPM7 with RNA interference or pharmacological agents not only reversed the EGF-enhanced migration of A549 cells but also inhibited the basal migration of A549 cells in the absence of EGF. Thus it seems that TRPM7 plays a pivotal role in the migration of A549 cells induced by EGF and thus could be a potential therapeutic target in lung cancers. (C) 2011 Elsevier Ltd. All rights reserved.