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Phosphoglycerate Mutase 1 Coordinates Glycolysis and Biosynthesis to Promote Tumor Growth

Journal Article · · Cancer Cell
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  1. Emory Univ. School of Medicine, Atlanta, GA (United States)
  2. Univ. of Chicago, IL (United States)
  3. Cell Signaling Technology, Inc., Danvers, MA (United States)
  4. Princeton Univ., NJ (United States)
  5. UT Southwestern Medical Center, Dallas, TX (United States)
  6. Northwestern Univ., Evanston, IL (United States)
  7. Novartis Inst. for BioMedical Research, Cambridge, MA (United States)
  8. Yale Univ. School of Medicine, New Haven, CT (United States)
+ Show Author Affiliations

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 partially 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.

Research Organization:
Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
Sponsoring Organization:
USDOE Office of Science (SC)
OSTI ID:
1056689
Journal Information:
Cancer Cell, Journal Name: Cancer Cell Journal Issue: 5 Vol. 22; ISSN 1535-6108
Publisher:
Elsevier
Country of Publication:
United States
Language:
ENGLISH

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES