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Kv10.1钾通道:从大脑到肿瘤

Kv10.1 potassium channel: from the brain to the tumors.

作者信息

Cázares-Ordoñez V, Pardo L A

机构信息

Oncophysiology Group, Max Planck Institute of Experimental Medicine, Hermann-Rein-Strasse 3, 37075 Göttingen, Germany.

出版信息

Biochem Cell Biol. 2017 Oct;95(5):531-536. doi: 10.1139/bcb-2017-0062. Epub 2017 Jul 14.

Abstract

The KCNH1 gene encodes the Kv10.1 (Eag1) ion channel, a member of the EAG (ether-à-go-go) family of voltage-gated potassium channels. Recent studies have demonstrated that KCHN1 mutations are implicated in Temple-Baraitser and Zimmermann-Laband syndromes and other forms of developmental deficits that all present with mental retardation and epilepsy, suggesting that Kv10.1 might be important for cognitive development in humans. Although the Kv10.1 channel is mainly expressed in the mammalian brain, its ectopic expression occurs in 70% of human cancers. Cancer cells and tumors expressing Kv10.1 acquire selective advantages that favor cancer progression through molecular mechanisms that involve several cellular pathways, indicating that protein-protein interactions may be important for Kv10.1 influence in cell proliferation and tumorigenesis. Several studies on transcriptional and post-transcriptional regulation of Kv10.1 expression have shown interesting mechanistic insights about Kv10.1 role in oncogenesis, increasing the importance of identifying the cellular factors that regulate Kv10.1 expression in tumors.

摘要

KCNH1基因编码Kv10.1(Eag1)离子通道,它是电压门控钾通道EAG(去极化)家族的成员。最近的研究表明,KCHN1突变与坦普尔 - 巴拉伊泽综合征和齐默尔曼 - 拉班德综合征以及其他形式的发育缺陷有关,这些缺陷都表现为智力迟钝和癫痫,这表明Kv10.1可能对人类认知发展很重要。虽然Kv10.1通道主要在哺乳动物大脑中表达,但其异位表达出现在70%的人类癌症中。表达Kv10.1的癌细胞和肿瘤通过涉及多种细胞途径的分子机制获得有利于癌症进展的选择性优势,这表明蛋白质 - 蛋白质相互作用可能对Kv10.1在细胞增殖和肿瘤发生中的影响很重要。几项关于Kv10.1表达的转录和转录后调控的研究已经揭示了Kv10.1在肿瘤发生中的作用机制,这增加了识别调节肿瘤中Kv10.1表达的细胞因子的重要性。

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