文章：

癌症是由尼古丁乙酰胆碱受体信号改变引发的吗？

Is cancer triggered by altered signalling of nicotinic acetylcholine receptors?

原文发布日期：2009-02-05

DOI: 10.1038/nrc2590

类型: Review Article

开放获取: 否

要点：

1. Nicotinic acetylcholine receptors (nAChRs) are ion channels that are expressed in the plasma membrane of all mammalian cells, including cancer cells.
2. nAChRs are central regulators that stimulate the synthesis and release of stimulatory and inhibitory neurotransmitters, which in turn regulate the release of growth, angiogenic and neurogenic factors and stimulate signal transduction in a cell-type-specific manner.
3. Chronic exposure to nicotine or nicotine-derived carcinogenic nitrosamines upregulates cancer-stimulatory nAChRs and desensitizes cancer-inhibitory nAChRs.
4. The homomeric α7nAChR is the major stimulator of cancer development and progression: it induces the synthesis and release of autocrine growth factors in small-cell lung cancer and indirectly stimulates most other types of cancer through the systemic and cellular release of stress neurotransmitters that bind as agonists to β-adrenergic receptors.
5. The heteromeric α4β2nAChR is a major inhibitor of cancer development and progression: it stimulates the release of γ-aminobutyric acid, which blocks the cancer stimulating effects of β-adrenergic receptors by inhibiting cyclic AMP.
6. Marker-guided cancer intervention strategies that target nAChRs and their effectors that aim to restore the balance between stimulatory and inhibitory neurotransmitters need to be developed.

要点翻译：

1. 烟碱型乙酰胆碱受体（nAChRs）是表达于所有哺乳动物细胞（包括癌细胞）质膜上的离子通道。
2. nAChRs是核心调控因子，能刺激兴奋性和抑制性神经递质的合成与释放，进而以细胞类型特异性方式调控生长因子、血管生成因子和神经生成因子的释放，并激活信号转导。
3. 长期暴露于尼古丁或尼古丁衍生的致癌亚硝胺会上调促癌nAChRs，并使抑癌nAChRs脱敏。
4. 同聚体α7nAChR是癌症发生与进展的主要刺激因子：它诱导小细胞肺癌中自分泌生长因子的合成与释放，并通过结合β-肾上腺素能受体激动剂的系统性及细胞性应激神经递质释放，间接刺激大多数其他类型癌症。
5. 异聚体α4β2nAChR是癌症发生与进展的主要抑制因子：它刺激γ-氨基丁酸的释放，通过抑制环磷腺苷阻断β-肾上腺素能受体的促癌效应。
6. 需要开发以nAChRs及其效应器为靶点的标志物指导的癌症干预策略，旨在恢复兴奋性与抑制性神经递质之间的平衡。

英文摘要：

Nicotinic acetylcholine receptors (nAChRs) are the central regulators of stimulatory and inhibitory neurotransmitters that control the synthesis and release of growth, angiogenic and neurotrophic factors in cancer cells, the cancer microenvironment and distant organs. Data discussed in this Review suggests that smoking and possibly other environmental and lifestyle factors increase the function of nAChRs that stimulate cancer cells and reduce the function of nAChRs that inhibit cancer cells. This novel paradigm necessitates the development of marker-guided cancer intervention strategies that aim to restore the balance between nAChR-mediated stimulatory and inhibitory neurotransmitters and their downstream effectors.

摘要翻译： 

烟碱型乙酰胆碱受体（nAChRs）是调控兴奋性和抑制性神经递质的中心环节，这些神经递质控制癌细胞、肿瘤微环境及远端器官中生长、血管生成和神经营养因子的合成与释放。本综述讨论的数据表明，吸烟以及可能的其他环境和生活方式因素会增强刺激癌细胞的nAChRs功能，同时削弱抑制癌细胞的nAChRs功能。这一新范式要求发展以标志物为指导的癌症干预策略，旨在恢复nAChR介导的兴奋性与抑制性神经递质及其下游效应器之间的平衡。

原文链接：

Is cancer triggered by altered signalling of nicotinic acetylcholine receptors?