Department of Pharmacology, School of Medicine, University of California, Irvine, Irvine, California 92697, USA.
Nat Rev Cancer. 2009 Dec;9(12):886-96. doi: 10.1038/nrc2747.
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.
昼夜节律调控着多种代谢和生理功能。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,构成生物钟的几个分子齿轮已被发现与细胞周期的调节剂建立了功能相互作用,而时钟功能的改变可能导致异常的细胞增殖。此外,还发现了昼夜节律钟与细胞代谢之间的联系,这些联系受染色质重塑的调控。这表明癌症中的代谢异常也可能是昼夜节律钟紊乱的结果。因此,全面了解将昼夜节律钟与细胞周期和代谢联系起来的分子联系,可能会为对抗某些人类肿瘤提供治疗益处。