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Journal of Oncology
Volume 2014 (2014), Article ID 524101, 13 pages
http://dx.doi.org/10.1155/2014/524101
Review Article

Phosphoglycerate Dehydrogenase: Potential Therapeutic Target and Putative Metabolic Oncogene

1Center 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
2Department of Biochemistry and Molecular Biology, The Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA

Received 4 August 2014; Revised 14 November 2014; Accepted 18 November 2014; Published 9 December 2014

Academic Editor: Rolf Bjerkvig

Copyright © 2014 Cheryl K. Zogg. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.