Zhao Yue
Center of Cell biology and Cancer Research, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USA.
J Oncol. 2016;2016:9650481. doi: 10.1155/2016/9650481. Epub 2016 Feb 14.
Nicotinic acetylcholine receptors (nAChRs) are ion channels that are expressed in the cell membrane of all mammalian cells, including cancer cells. Recent findings suggest that nAChRs not only mediate nicotine addiction in the brain but also contribute to the development and progression of cancers directly induced by nicotine and its derived carcinogenic nitrosamines whereas deregulation of the nAChRs is observed in many cancers, and genome-wide association studies (GWAS) indicate that SNPs nAChRs associate with risks of lung cancers and nicotine addiction. Emerging evidences suggest nAChRs are posited at the central regulatory loops of numerous cell growth and prosurvival signal pathways and also mediate the synthesis and release of stimulatory and inhibitory neurotransmitters induced by their agonists. Thus nAChRs mediated cell signaling plays an important role in stimulating the growth and angiogenic and neurogenic factors and mediating oncogenic signal transduction during cancer development in a cell type specific manner. In this review, we provide an integrated view of nAChRs signaling in cancer, heightening on the oncogenic properties of nAChRs that may be targeted for cancer treatment.
烟碱型乙酰胆碱受体(nAChRs)是一种离子通道,存在于包括癌细胞在内的所有哺乳动物细胞的细胞膜中。最近的研究发现表明,nAChRs不仅介导大脑中的尼古丁成瘾,还直接促进由尼古丁及其衍生的致癌亚硝胺诱发的癌症的发展和进程,而在许多癌症中都观察到nAChRs的失调,全基因组关联研究(GWAS)表明nAChRs的单核苷酸多态性(SNPs)与肺癌风险和尼古丁成瘾有关。新出现的证据表明,nAChRs处于众多细胞生长和促生存信号通路的核心调控环中,并且还介导其激动剂诱导的刺激性和抑制性神经递质的合成与释放。因此,nAChRs介导的细胞信号传导在以细胞类型特异性方式刺激癌症发展过程中的生长、血管生成和神经生成因子以及介导致癌信号转导方面发挥着重要作用。在本综述中,我们提供了nAChRs在癌症中信号传导的综合观点,着重阐述了可能作为癌症治疗靶点的nAChRs的致癌特性。