Ion transporters in brain tumors.

Ion transporters in brain tumors.
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DOI:
10.2174/0929867322666150114151946
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发表时间:
2015
影响因子:
4.1
通讯作者:
Sun D
Sun D
中科院分区:
医学3区
文献类型:
--
作者:
Cong D;Zhu W;Kuo JS;Hu S;Sun D

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在生理条件下,离子转运体在调节离子稳态、细胞体积和细胞信号转导中起着重要的作用。它们最近在癌症发展过程中扮演了重要角色。本文综述了多形性胶质母细胞瘤(GBM)和其他恶性肿瘤中两种重要的离子转运蛋白——钠-钾-氯化钾共转运蛋白异构体1 (NKCC-1)和钠-氢交换蛋白异构体1 (NHE-1)。NKCC-1是一种Na+依赖的Cl -转运蛋白,介导Na+、K+和Cl -离子在质膜上的运动,维持细胞体积和细胞内K+和Cl -稳态。NHE-1是一种普遍表达的细胞膜蛋白,它调节细胞内pH (pHi)和细胞外微域pH (pHe)稳态和细胞体积。本文总结了近年来NKCC-1和NHE-1在GBM及乳腺癌、肝细胞癌、肺癌等恶性肿瘤中的临床前实验研究。这些研究表明,药物抑制或下调这些离子转运蛋白可减少癌细胞的增殖,增加细胞凋亡,抑制癌细胞的迁移和侵袭。这些新发现揭示了这些离子转运体作为癌症诊断和/或治疗的新靶点的潜力。
Ion transporters are important in regulation of ionic homeostasis, cell volume, and cellular signal transduction under physiological conditions. They have recently emerged as important players in cancer progression. In this review, we discussed two important ion transporter proteins, sodium-potassium-chloride cotransporter isoform 1 (NKCC-1) and sodium-hydrogen exchanger isoform 1 (NHE-1) in Glioblastoma multiforme (GBM) and other malignant tumors. NKCC-1 is a Na+-dependent Cl− transporter that mediates the movement of Na+, K+, and Cl− ions across the plasma membrane and maintains cell volume and intracellular K+ and Cl− homeostasis. NHE-1 is a ubiquitously expressed cell membrane protein which regulates intracellular pH (pHi) and extracellular microdomain pH (pHe) homeostasis and cell volume. Here, we summarized recent pre-clinical experimental studies on NKCC-1 and NHE-1 in GBM and other malignant tumors, such as breast cancer, hepatocellular carcinoma, and lung cancer. These studies illustrated that pharmacological inhibition or down-regulation of these ion transporter proteins reduces proliferation, increases apoptosis, and suppresses migration and invasion of cancer cells. These new findings reveal the potentials of these ion transporters as new targets for cancer diagnosis and/or treatment.
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