HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Phosphoglycerate mutase 1 coordinates glycolysis and biosynthesis to promote tumor growth.

Abstract
It is unclear how cancer cells coordinate glycolysis and biosynthesis to support rapidly growing tumors. We found that the glycolytic enzyme phosphoglycerate mutase 1 (PGAM1), commonly upregulated in human cancers due to loss of TP53, contributes to biosynthesis regulation in part by controlling intracellular levels of its substrate, 3-phosphoglycerate (3-PG), and product, 2-phosphoglycerate (2-PG). 3-PG binds to and inhibits 6-phosphogluconate dehydrogenase in the oxidative pentose phosphate pathway (PPP), while 2-PG activates 3-phosphoglycerate dehydrogenase to provide feedback control of 3-PG levels. Inhibition of PGAM1 by shRNA or a small molecule inhibitor PGMI-004A results in increased 3-PG and decreased 2-PG levels in cancer cells, leading to significantly decreased glycolysis, PPP flux and biosynthesis, as well as attenuated cell proliferation and tumor growth.
AuthorsTaro Hitosugi, Lu Zhou, Shannon Elf, Jun Fan, Hee-Bum Kang, Jae Ho Seo, Changliang Shan, Qing Dai, Liang Zhang, Jianxin Xie, Ting-Lei Gu, Peng Jin, Masa Alečković, Gary LeRoy, Yibin Kang, Jessica A Sudderth, Ralph J DeBerardinis, Chi-Hao Luan, Georgia Z Chen, Susan Muller, Dong M Shin, Taofeek K Owonikoko, Sagar Lonial, Martha L Arellano, Hanna J Khoury, Fadlo R Khuri, Benjamin H Lee, Keqiang Ye, Titus J Boggon, Sumin Kang, Chuan He, Jing Chen
JournalCancer cell (Cancer Cell) Vol. 22 Issue 5 Pg. 585-600 (Nov 13 2012) ISSN: 1878-3686 [Electronic] United States
PMID23153533 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2012 Elsevier Inc. All rights reserved.
Chemical References
  • Gluconates
  • Glyceric Acids
  • 2-phosphoglycerate
  • 3-phosphoglycerate
  • Glucosephosphate Dehydrogenase
  • Phosphoglycerate Mutase
  • 6-phosphogluconic acid
Topics
  • Animals
  • Binding, Competitive
  • Cell Line, Tumor
  • Cell Proliferation
  • Enzyme Activation
  • Gene Knockdown Techniques
  • Gluconates (metabolism)
  • Glucosephosphate Dehydrogenase (metabolism)
  • Glyceric Acids (metabolism)
  • Glycolysis (genetics, physiology)
  • Humans
  • Mice
  • Mice, Nude
  • Models, Molecular
  • Neoplasms (enzymology, pathology)
  • Phosphoglycerate Mutase (antagonists & inhibitors, genetics, metabolism, physiology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: