Regulation of voltage-gated sodium channel expression in cancer: hormones, growth factors and auto-regulation.
Regulation of voltage-gated sodium channel expression in cancer: hormones, growth factors and auto-regulation.
复制标题
调节癌症电压门控通道表达：激素，生长因子和自身调节。
DOI：
10.1098/rstb.2013.0105
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发表时间：
2014-03-19
期刊：
影响因子：
--
通讯作者：
Djamgoz MB
中科院分区：
文献类型：
--
作者：
Fraser SP;Ozerlat-Gunduz I;Brackenbury WJ;Fitzgerald EM;Campbell TM;Coombes RC;Djamgoz MB
尽管越来越多的体外和体内癌细胞中发现了离子通道，并显示出对癌症过程的不同方面和阶段有贡献，但对控制其表达的机制知之甚少。在这里，我们专注于电压门控Na+通道（VGSC），在许多类型的癌症中上调，它们的活性增强细胞行为，成为转移级联反应的组成部分。VGSC的调节发生在从转录到翻译后的层级水平。重要的是，主流癌症机制，特别是激素和生长因子，在调节中发挥重要作用。总的来说，在主要的激素敏感性癌症中，如乳腺癌和前列腺癌，基因组类固醇激素敏感性和功能性VGSC表达之间存在负相关。通过正反馈的活性依赖性调节已经在强转移性细胞中得到证实，由此VGSC是自我维持的，其活性促进进一步的功能通道表达。这种自动调节与正常细胞不同，在正常细胞中，活性依赖性调节主要通过负反馈发生。在整个过程中，我们强调了功能性VGSC表达和调节在癌症中可能的临床意义。
Although ion channels are increasingly being discovered in cancer cells in vitro and in vivo, and shown to contribute to different aspects and stages of the cancer process, much less is known about the mechanisms controlling their expression. Here, we focus on voltage-gated Na+ channels (VGSCs) which are upregulated in many types of carcinomas where their activity potentiates cell behaviours integral to the metastatic cascade. Regulation of VGSCs occurs at a hierarchy of levels from transcription to post-translation. Importantly, mainstream cancer mechanisms, especially hormones and growth factors, play a significant role in the regulation. On the whole, in major hormone-sensitive cancers, such as breast and prostate cancer, there is a negative association between genomic steroid hormone sensitivity and functional VGSC expression. Activity-dependent regulation by positive feedback has been demonstrated in strongly metastatic cells whereby the VGSC is self-sustaining, with its activity promoting further functional channel expression. Such auto-regulation is unlike normal cells in which activity-dependent regulation occurs mostly via negative feedback. Throughout, we highlight the possible clinical implications of functional VGSC expression and regulation in cancer.
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DOI：
10.4161/chan.21910
发表时间：
2012-09
期刊：
Channels (Austin, Tex.)
影响因子：
--
作者：
Brackenbury WJ
通讯作者：
Brackenbury WJ
影响因子：
4.8
作者：
Andrikopoulos, Petros;Fraser, Scott P.;Djamgoz, Mustafa B. A.
通讯作者：
Djamgoz, Mustafa B. A.
影响因子：
4.5
作者：
Bennett, ES;Smith, BA;Harper, JM
通讯作者：
Harper, JM
影响因子：
10.8
作者：
Boehmer, C;Wilhelm, V;Lang, F
通讯作者：
Lang, F
影响因子：
3.6
作者：
Barann, M;Göthert, M;Bönisch, H
通讯作者：
Bönisch, H