Center for Epigenetics and Metabolism, U1233 INSERM, Department of Biological Chemistry, University of California, Irvine, CA, USA.
Department of Endocrinology, Metabolism, and Nephrology, School of Medicine, Keio University, Tokyo, Japan.
Nat Rev Cancer. 2020 Nov;20(11):645-661. doi: 10.1038/s41568-020-0291-9. Epub 2020 Sep 7.
Circadian rhythms govern a large array of physiological and metabolic functions. Perturbations of the daily cycle have been linked to elevated risk of developing cancer as well as poor prognosis in patients with cancer. Also, expression of core clock genes or proteins is remarkably attenuated particularly in tumours of a higher stage or that are more aggressive, possibly linking the circadian clock to cellular differentiation. Emerging evidence indicates that metabolic control by the circadian clock underpins specific hallmarks of cancer metabolism. Indeed, to support cell proliferation and biomass production, the clock may direct metabolic processes of cancer cells in concert with non-clock transcription factors to control how nutrients and metabolites are utilized in a time-specific manner. We hypothesize that the metabolic switch between differentiation or stemness of cancer may be coupled to the molecular clockwork. Moreover, circadian rhythms of host organisms appear to dictate tumour growth and proliferation. This Review outlines recent discoveries of the interplay between circadian rhythms, proliferative metabolism and cancer, highlighting potential opportunities in the development of future therapeutic strategies.
昼夜节律调控着大量生理和代谢功能。每日节律的紊乱与癌症风险的增加以及癌症患者预后不良有关。此外，核心时钟基因或蛋白的表达在更高分期或更具侵袭性的肿瘤中显著减弱，这可能将生物钟与细胞分化联系起来。新出现的证据表明，昼夜节律对代谢的控制是癌症代谢特定特征的基础。事实上，为了支持细胞增殖和生物量的产生，时钟可能会与非时钟转录因子一起指导癌细胞的代谢过程，以控制营养物质和代谢物如何以特定的时间方式被利用。我们假设，癌症的分化或干性之间的代谢转变可能与分子时钟有关。此外，宿主生物的昼夜节律似乎决定着肿瘤的生长和增殖。本综述概述了昼夜节律、增殖代谢和癌症之间相互作用的最新发现，强调了未来治疗策略发展中的潜在机会。
