Ion channels and tranporters in cancer. 2. Ion channels and the control of cancer cell migration
Ion channels and tranporters in cancer. 2. Ion channels and the control of cancer cell migration
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DOI：
10.1152/ajpcell.00102.2011
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发表时间：
2011-09-01
影响因子：
5.5
通讯作者：
Sontheimer, Harald
中科院分区：
文献类型：
--
作者：
Cuddapah, Vishnu Anand;Sontheimer, Harald
Cuddapah VA，Sontheimer H.癌症中的离子通道和转运蛋白。2.离子通道与癌细胞迁移的控制。美国生理学杂志细胞生理学301：C541-C549，2011年。首次发表于2011年5月4日; doi：10.1152/ajpcell.00102.2011。高度恶性肿瘤的一个标志是恶性细胞能够侵入未受影响的组织并传播疾病。这在神经胶质瘤中尤其明显，神经胶质瘤是影响成人的最常见和致命的原发性脑癌。迁移的细胞遇到有限的空间，并似乎能够调整其形状，以适应狭窄的细胞外空间。越来越多的工作表明，离子通道和转运蛋白促进了细胞迁移/侵袭。新出现的概念是K+和Cl-起着吸附活性离子的作用，它们与义务水一起穿过质膜，从而调节细胞的形状和体积。在神经胶质瘤细胞中，Na+-K+-Cl-协同转运蛋白（NKCC 1）积极积累K+和Cl-，建立KCl流出的梯度。Ca 2+激活的K+通道和电压门控Cl-通道主要负责外排KCl促进流体动力学体积变化。在其他癌症中，不同的K+或甚至Na-通道可能与各种Cl-通道一起发挥作用，以支持类似的体积变化。参与迁移的通道通常由Ca 2+信号传导调节，最有可能将细胞外刺激与细胞迁移偶联。重要的是，离子通道和转运蛋白的抑制似乎与癌症的治疗临床相关。最近的临床前数据表明，用FDA批准的药物抑制NKCC 1可以减少肿瘤迁移。此外，正在进行的临床试验表明，氯离子通道抑制剂可能是治疗神经胶质瘤的一种疗法。这里回顾的数据强烈表明，离子通道是一个有前途的目标，为发展新的治疗方法，以打击癌症。
Cuddapah VA, Sontheimer H. Ion channels and tranporters in cancer. 2. Ion channels and the control of cancer cell migration. Am J Physiol Cell Physiol 301: C541-C549, 2011. First published May 4, 2011; doi: 10.1152/ajpcell.00102.2011.-A hallmark of high-grade cancers is the ability of malignant cells to invade unaffected tissue and spread disease. This is particularly apparent in gliomas, the most common and lethal type of primary brain cancer affecting adults. Migrating cells encounter restricted spaces and appear able to adjust their shape to accommodate to narrow extracellular spaces. A growing body of work suggests that cell migration/invasion is facilitated by ion channels and transporters. The emerging concept is that K+ and Cl- function as osmotically active ions, which cross the plasma membrane in concert with obligated water thereby adjusting a cell's shape and volume. In glioma cells Na+-K+-Cl- cotransporters (NKCC1) actively accumulate K+ and Cl-, establishing a gradient for KCl efflux. Ca2+-activated K+ channels and voltage-gated Cl- channels are largely responsible for effluxing KCl promoting hydrodynamic volume changes. In other cancers, different K+ or even Na- channels may function in concert with a variety of Cl- channels to support similar volume changes. Channels involved in migration are frequently regulated by Ca2+ signaling, most likely coupling extracellular stimuli to cell migration. Importantly, the inhibition of ion channels and transporters appears to be clinically relevant for the treatment of cancer. Recent preclinical data indicates that inhibition of NKCC1 with an FDA-approved drug decreases neoplastic migration. Additionally, ongoing clinical trials demonstrate that an inhibitor of chloride channels may be a therapy for the treatment of gliomas. Data reviewed here strongly indicate that ion channels are a promising target for the development of novel therapeutics to combat cancer.