Clinical Biochemistry Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
Stem Cell Unit, King Fahad Medical Research Center, Jeddah, Saudi Arabia.
Bioessays. 2021 Apr;43(4):e2000205. doi: 10.1002/bies.202000205. Epub 2021 Feb 2.
It is not clear why cancer cells choose to disrupt their circadian clock rhythms, and whether such disruption governs a selective fitness and a survival advantage. In this review, I focus on understanding the impacts of clock gene disruption on a simpler model, such as the unicellular cyanobacterium, in order to explain how cancer cells may alter the circadian rhythm to reprogram their metabolism based on their needs and status. It appears to be that the activation of the oxidative pentose phosphate pathway (OPPP) and production of NADPH, the preferred molecule for detoxification of reactive oxygen species, is a critical process for night survival in unicellular organisms. The circadian clock acts as a gatekeeper that controls how the organism will utilize its sugar, shifting sugar influx between glycolysis and OPPP. The circadian clock can thus act as a gatekeeper between an anabolic, proliferative mode and a homeostatic, survival mode.
目前尚不清楚癌细胞为何会选择打乱生物钟节律，以及这种打乱是否会带来选择性适应和生存优势。在这篇综述中，我专注于了解生物钟基因破坏对更简单模型（如单细胞蓝藻）的影响，以便解释癌细胞如何根据自身需求和状态改变生物钟节律以重新编程代谢。似乎激活氧化戊糖磷酸途径（OPPP）并产生 NADPH，即用于清除活性氧的首选分子，是单细胞生物夜间生存的关键过程。生物钟充当了一个调控器，控制着生物体将如何利用其糖分，在糖酵解和 OPPP 之间转换糖的流入。因此，生物钟可以作为合成代谢、增殖模式和体内平衡、生存模式之间的调控器。
