Institute of Molecular Medicine, MD Anderson/UTHealth Graduate School for Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, RX 77030, USA.
J Biochem. 2022 May 11;171(5):477-486. doi: 10.1093/jb/mvac017.
There is growing evidence that disruption of our 24-h clock increases our risk for acquiring several diseases and disorders. One of these diseases is cancer. While the mechanistic links between circadian clock disruption and cancer initiation or progression are an active area of study, significantly more work needs to be done to understand the molecular substrates involved. Of particular complexity remains the functions of the clock in individual cells during the process of transformation (cancer initiation) versus the functions of the clock in tumour-surrounding stroma in the process of tumour progression or metastasis. Indeed, the nexus of cellular circadian dynamics, metabolism and carcinogenesis is drawing more attention, and many new studies are now highlighting the critical role of circadian rhythms and clock proteins in cancer prevention. In this brief review, we cover some of the basic mechanisms reported to link circadian disruption and cancer at the level of gene expression and metabolism. We also review some of the human studies addressing circadian disruption and cancer incidence as well as some controlled laboratory studies connecting the two in pre-clinical models. Finally, we discuss the tremendous opportunity to use circadian approaches for future prevention and treatment in the context of cancer in specific organs.
越来越多的证据表明，我们 24 小时生物钟的紊乱会增加我们患上几种疾病和障碍的风险。其中一种疾病是癌症。虽然生物钟紊乱与癌症的发生或进展之间的机制联系是一个活跃的研究领域，但仍需要做更多的工作来了解涉及的分子底物。特别复杂的是，时钟在单个细胞转化（癌症发生）过程中的功能与时钟在肿瘤进展或转移过程中在肿瘤周围基质中的功能。事实上，细胞昼夜节律动力学、代谢和致癌作用的联系引起了更多的关注，许多新的研究现在强调了昼夜节律和时钟蛋白在癌症预防中的关键作用。在这篇简短的综述中，我们介绍了一些报告的基本机制，这些机制将生物钟紊乱与基因表达和代谢水平上的癌症联系起来。我们还回顾了一些针对生物钟紊乱与癌症发病率的人类研究，以及一些将两者在临床前模型中联系起来的对照实验室研究。最后，我们讨论了在特定器官的癌症背景下，利用昼夜节律方法进行未来预防和治疗的巨大机会。
