文章：

新陈代谢和癌症：生物钟的联系

Metabolism and cancer: the circadian clock connection

原文发布日期：2009-12-01

DOI: 10.1038/nrc2747

类型: Review Article

开放获取: 否

要点：

1. Circadian rhythms are endogenously generated rhythms that occur with a periodicity of around 24 hours.
2. There is an intimate link between the disruption of circadian rhythms and cancer. The circadian clock regulates key aspects of cell growth and survival, including the cell cycle, DNA damage responses, cellular senescence and metabolism.
3. Several cell cycle genes, such as WEE1, MYC and cyclin D1, are regulated by the circadian clock. This could be one way by which the circadian clock gates cell division.
4. Key clock proteins, such as PER1 and timeless, interact with proteins involved in the DNA damage responses. DNA damage itself can reset the clock.
5. Cellular metabolism is altered in cancer. Several key metabolic genes are under circadian regulation. Recent findings that SIRT1, a key regulator of metabolism, is an integral part of the clock machinery suggest that the circadian clock can regulate cellular metabolism in multiple ways.
6. The transcriptional negative feedback loop that regulates the circadian clock is interlocked with an enzymatic feedback loop in which SIRT1 regulates the levels of its own cofactor, NAD⁺.

要点翻译：

1. 昼夜节律是一种内源性生成的节律，其周期约为24小时。
2. 昼夜节律紊乱与癌症之间存在密切联系。生物钟调控细胞生长和存活的关键环节，包括细胞周期、DNA损伤应答、细胞衰老及代谢。
3. WEE1、MYC和细胞周期蛋白D1等若干细胞周期基因受昼夜节律调控，这可能是生物钟控制细胞分裂的途径之一。
4. PER1和timeless等关键时钟蛋白与DNA损伤应答相关蛋白存在相互作用，而DNA损伤本身可重置生物钟。
5. 癌症中细胞代谢会发生改变。多个关键代谢基因受昼夜节律调控。最新研究发现代谢关键调控因子SIRT1是生物钟机制的内在组成部分，这表明昼夜节律可通过多种方式调控细胞代谢。
6. 调控昼夜节律的转录负反馈环路与酶促反馈环路相互耦联，其中SIRT1可调控其自身辅因子NAD+的水平。

英文摘要：

Circadian rhythms govern a remarkable variety of metabolic and physiological functions. Accumulating epidemiological and genetic evidence indicates that the disruption of circadian rhythms might be directly linked to cancer. Intriguingly, several molecular gears constituting the clock machinery have been found to establish functional interplays with regulators of the cell cycle, and alterations in clock function could lead to aberrant cellular proliferation. In addition, connections between the circadian clock and cellular metabolism have been identified that are regulated by chromatin remodelling. This suggests that abnormal metabolism in cancer could also be a consequence of a disrupted circadian clock. Therefore, a comprehensive understanding of the molecular links that connect the circadian clock to the cell cycle and metabolism could provide therapeutic benefit against certain human neoplasias.

摘要翻译： 

昼夜节律调控着众多代谢与生理功能。越来越多的流行病学和遗传学证据表明，昼夜节律的破坏可能与癌症直接相关。有趣的是，时钟机制中的若干分子齿轮已被发现能与细胞周期调控因子形成功能性相互作用，而时钟功能的异常可导致细胞增殖失控。此外，研究还揭示了昼夜时钟与细胞代谢之间通过染色质重塑实现的关联，提示癌症中的代谢异常也可能是昼夜节律紊乱的后果。因此，全面理解昼夜时钟与细胞周期及代谢之间的分子联系，有望为某些人类肿瘤的治疗带来益处。

原文链接：

Metabolism and cancer: the circadian clock connection