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

被引:118
作者
Gao, Haixia [1 ,2 ]
Chen, Xingjuan [1 ,2 ]
Du, Xiaona [1 ,2 ]
Guan, Bingcai [1 ,2 ]
Liu, Yani [1 ,2 ]
Zhang, Hailin [1 ,2 ]
机构
[1] Hebei Med Univ, Dept Pharmacol, Key Lab Pharmacol & Toxicol New Drugs, Shijiazhuang 050017, Peoples R China
[2] Hebei Med Univ, Minist Educ, Key Lab Neural & Vasc Biol, Shijiazhuang 050017, Peoples R China
基金
中国国家自然科学基金;
关键词
TRPM7; EGF; Lung cancer; Migration; CHEMOTHERAPY-NAIVE PATIENTS; LUNG-CANCER; TYROSINE KINASE; CATION CHANNEL; PHASE-II; RECEPTOR; GROWTH; CALCIUM; GEFITINIB; MG2+;
D O I
10.1016/j.ceca.2011.09.003
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
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.
引用
收藏
页码:559 / 568
页数:10
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