Phosphoglycerate mutase 1 coordinates glycolysis and biosynthesis to promote tumor growth

Cancer Cell. 2012 Nov 13;22(5):585-600. doi: 10.1016/j.ccr.2012.09.020.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Binding, Competitive
  • Cell Line, Tumor
  • Cell Proliferation
  • Enzyme Activation
  • Gene Knockdown Techniques
  • Gluconates / metabolism
  • Glucosephosphate Dehydrogenase / metabolism
  • Glyceric Acids / metabolism
  • Glycolysis / genetics
  • Glycolysis / physiology*
  • Humans
  • Mice
  • Mice, Nude
  • Models, Molecular
  • Neoplasms / enzymology*
  • Neoplasms / pathology
  • Phosphoglycerate Mutase / antagonists & inhibitors
  • Phosphoglycerate Mutase / genetics
  • Phosphoglycerate Mutase / metabolism
  • Phosphoglycerate Mutase / physiology*


  • Gluconates
  • Glyceric Acids
  • 2-phosphoglycerate
  • 3-phosphoglycerate
  • Glucosephosphate Dehydrogenase
  • Phosphoglycerate Mutase
  • 6-phosphogluconic acid