Zogg Cheryl K
Center for Surgery and Public Health, Harvard Medical School and Harvard School of Public Health, Department of Surgery, Brigham and Women's Hospital, 1620 Tremont Street, Boston, MA 02120, USA ; Department of Biochemistry and Molecular Biology, The Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA.
J Oncol. 2014;2014:524101. doi: 10.1155/2014/524101. Epub 2014 Dec 9.
Exemplified by cancer cells' preference for glycolysis, for example, the Warburg effect, altered metabolism in tumorigenesis has emerged as an important aspect of cancer in the past 10-20 years. Whether due to changes in regulatory tumor suppressors/oncogenes or by acting as metabolic oncogenes themselves, enzymes involved in the complex network of metabolic pathways are being studied to understand their role and assess their utility as therapeutic targets. Conversion of glycolytic intermediate 3-phosphoglycerate into phosphohydroxypyruvate by the enzyme phosphoglycerate dehydrogenase (PHGDH)-a rate-limiting step in the conversion of 3-phosphoglycerate to serine-represents one such mechanism. Forgotten since classic animal studies in the 1980s, the role of PHGDH as a potential therapeutic target and putative metabolic oncogene has recently reemerged following publication of two prominent papers near-simultaneously in 2011. Since that time, numerous studies and a host of metabolic explanations have been put forward in an attempt to understand the results observed. In this paper, I review the historic progression of our understanding of the role of PHGDH in cancer from the early work by Snell through its reemergence and rise to prominence, culminating in an assessment of subsequent work and what it means for the future of PHGDH.
例如，以癌细胞对糖酵解的偏好（即瓦伯格效应）为例，在过去10到20年里，肿瘤发生过程中代谢的改变已成为癌症的一个重要方面。无论是由于肿瘤抑制因子/癌基因调控的变化，还是这些参与复杂代谢途径网络的酶本身作为代谢癌基因发挥作用，人们正在对其进行研究，以了解它们的作用，并评估它们作为治疗靶点的效用。由磷酸甘油酸脱氢酶（PHGDH）将糖酵解中间产物3-磷酸甘油酸转化为磷酸羟基丙酮酸——这是3-磷酸甘油酸转化为丝氨酸的限速步骤——就是这样一种机制。自20世纪80年代经典动物研究以来被遗忘的PHGDH作为潜在治疗靶点和假定代谢癌基因的作用，在2011年两篇重要论文几乎同时发表后最近又重新出现。从那时起，人们提出了大量研究和一系列代谢解释，试图理解所观察到的结果。在本文中，我回顾了我们对PHGDH在癌症中作用的理解的历史进程，从斯内尔早期的工作到它的重新出现并崭露头角，最终对后续工作及其对PHGDH未来的意义进行评估。
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