The circadian clock in cancer development and therapy.
The circadian clock in cancer development and therapy.
复制标题
癌症发展和治疗中的生物钟。
DOI：
10.1016/b978-0-12-396971-2.00009-9
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发表时间：
2013
影响因子：
--
通讯作者：
Kettner, Nicole M.
中科院分区：
文献类型：
--
作者：
Fu, Loning;Kettner, Nicole M.
哺乳动物功能的大多数方面都显示出由内源性时钟驱动的昼夜节律。昼夜节律钟由基因操作，包括大脑中的一个中央时钟，该时钟对环境信号作出反应，并通过昼夜节律输出途径控制外周组织中的从属时钟。在体内，中枢和外周时钟以组织特异性的方式协调产生有节奏的基因表达，将各种生理和行为过程与环境的周期性变化结合起来。然而，随着世界工业化，利用外部昼夜节律线索破坏内源性体内平衡的活动有所增加。这种生活方式的改变与人类健康各个方面的疾病风险增加有关，包括癌症。人类和动物模型的研究表明，体内癌症的发展与能量平衡、免疫功能和衰老等昼夜节律稳态的丧失密切相关，而这些昼夜节律平衡是由细胞增殖、衰老、代谢和DNA损伤反应等对肿瘤抑制至关重要的细胞功能支持的。生物钟通过外周组织细胞的局部和细胞外信号在机体水平上控制这些细胞功能。因此，分层哺乳动物生物钟提供了一个独特的系统来研究癌变作为体内不受调节的生理过程。宿主和恶性组织在细胞增殖和代谢方面的不同步也为新的抗癌治疗提供了新的和令人兴奋的选择。
Most aspects of mammalian function display circadian rhythms driven by an endogenous clock. The circadian clock is operated by genes and comprises a central clock in the brain that responds to environmental cues and controls subordinate clocks in peripheral tissues via circadian output pathways. The central and peripheral clocks coordinately generate rhythmic gene expression in a tissue-specific manner in vivo to couple diverse physiological and behavioral processes to periodic changes in the environment. However, as the world industrialized, activities that disrupt endogenous homeostasis with external circadian cues have increased. This change in lifestyle has been linked to increased risk of diseases in all aspects of human health, including cancer. Studies in humans and animal models have revealed that cancer development in vivo is closely associated with the loss of circadian homeostasis in energy balance, immune function and aging that are supported by cellular functions important for tumor suppression including cell proliferation, senescence, metabolism and DNA damage response. The clock controls these cellular functions both locally in cells of peripheral tissues and at the organismal level via extracellular signaling. Thus, the hierarchical mammalian circadian clock provides a unique system to study carcinogenesis as a deregulated physiological process in vivo. The asynchrony between host and malignant tissues in cell proliferation and metabolism also provides new and exciting options for novel anti-cancer therapies.