文章：

生物钟：起搏器和肿瘤抑制器

The circadian clock: pacemaker and tumour suppressor

原文发布日期：2003-05-01

DOI: 10.1038/nrc1072

类型: Review Article

开放获取: 否

要点：

1. The circadian clock is the internal timing machine that can sustain rhythms of about 24 hours in the absence of external cues. The circadian clock is operated by the feedback loops of the circadian genes in the mammalian central pacemaker, as well as in most peripheral tissues.
2. The mammalian central pacemaker is located in the suprachiasmatic nuclei (SCN) of the brain and controls the activity of peripheral clocks through the neuroendocrine and autonomic nervous systems. The circadian clock regulates hundreds of functions in the human body.
3. Disruption of circadian rhythms has been linked to mammalian tumorigenesis and tumour progression, and has been used as an independent prognostic factor of survival time for patients with certain metastatic cancers.
4. Normal and malignant tissues often show asynchronies in cell proliferation and metabolic rhythms. Based on these observations, cancer chronotherapy has been developed to improve the efficacy in cancer treatment and the quality of patients' life.
5. The circadian clock functions in vivo as a tumour suppressor at the systemic, cellular and molecular levels. The central clock is capable of generating 24-hour cell-proliferation rhythms in peripheral tissues through the activity of the neuroendocrine and autonomic nervous systems.
6. Molecular clocks in peripheral tissues control cell-proliferation rhythms by regulating the expression of cell-cycle genes. The core circadian genes are also involved in regulating cell proliferation. The circadian clock in peripheral tissues responds directly to DNA damage and could be important in the control of the cell cycle and apoptosis.
7. The molecular clockworks and cell-cycle clocks in peripheral tissues can be regulated simultaneously by the central clock, through interacting signalling pathways. Further study of the mechanism of the circadian clock in tumour suppression and the DNA-damage response has important implications for cancer therapy.

要点翻译：

1. 生物钟是一种内部计时机制，能在缺乏外界信号的情况下维持约24小时的节律。哺乳动物的生物钟由中枢起搏器及大多数外周组织中的 circadian 基因反馈回路驱动。
2. 哺乳动物的中枢起搏器位于脑部视交叉上核（SCN），通过神经内分泌和自主神经系统调控外周生物钟的活动。生物钟调节着人体数百项功能。
3. 昼夜节律紊乱与哺乳动物肿瘤发生和进展相关，并已被用作某些转移性癌症患者生存期的独立预后因素。
4. 正常组织与恶性组织常在细胞增殖和代谢节律上表现出不同步性。基于这些发现，癌症时间疗法被开发用于提高癌症治疗效果并改善患者生活质量。
5. 生物钟在体内通过系统、细胞和分子水平发挥抑癌作用。中枢时钟通过神经内分泌和自主神经系统活动，能在外周组织中产生24小时周期的细胞增殖节律。
6. 外周组织中的分子时钟通过调控细胞周期基因表达来控制细胞增殖节律。核心生物钟基因也参与调节细胞增殖过程。外周组织中的生物钟能直接响应DNA损伤，在细胞周期和凋亡调控中具有重要作用。
7. 外周组织中的分子时钟系统与细胞周期时钟可通过交互信号通路同时受中枢时钟调控。进一步研究生物钟在肿瘤抑制和DNA损伤应答中的机制，对癌症治疗具有重要意义。

英文摘要：

The circadian rhythms are daily oscillations in various biological processes that are regulated by an endogenous clock. Disruption of these rhythms has been associated with cancer in humans. One of the cellular processes that is regulated by circadian rhythm is cell proliferation, which often shows asynchrony between normal and malignant tissues. This asynchrony highlights the importance of the circadian clock in tumour suppression in vivo and is one of the theoretical foundations for cancer chronotherapy. Investigation of the mechanisms by which the circadian clock controls cell proliferation and other cellular functions might lead to new therapeutic targets.

摘要翻译： 

昼夜节律是由内源性时钟调控的多种生物过程中的日常振荡。这些节律的紊乱与人类癌症的发生有关。昼夜节律调控的细胞过程之一是细胞增殖，在正常组织与恶性组织之间常表现出不同步性。这种不同步性突显了昼夜时钟在体内肿瘤抑制中的重要性，也是癌症时间疗法的理论基础之一。研究昼夜时钟如何调控细胞增殖及其他细胞功能的机制，可能带来新的治疗靶点。

原文链接：

The circadian clock: pacemaker and tumour suppressor