Phosphoglycerate Mutase 1 Coordinates Glycolysis and Biosynthesis to Promote Tumor Growth

Journal Article · Mon Nov 12 00:00:00 EST 2012 · Cancer Cell

DOI:https://doi.org/10.1016/j.ccr.2012.09.020· OSTI ID:1056689

Hitosugi, Taro ^[1]; Zhou, Lu ^[2]; Elf, Shannon ^[1]; Fan, Jun ^[1]; Kang, Hee-Bum ^[1]; Seo, Jae Ho ^[1]; Shan, Changliang ^[1]; Dai, Qing ^[2]; Zhang, Liang ^[2]; Xie, Jianxin ^[3]; Gu, Ting-Lei ^[3]; Jin, Peng ^[1]; Alečković, Masa ^[4]; LeRoy, Gary ^[4]; Kang, Yibin ^[4]; Sudderth, Jessica A. ^[5]; DeBerardinis, Ralph J. ^[5]; Luan, Chi-Hao ^[6]; Chen, Georgia Z. ^[1]; Muller, Susan ^[1] ; Shin, Dong M. ^[1]; Owonikoko, Taofeek K. ^[1]; Lonial, Sagar ^[1]; Arellano, Martha L. ^[1]; Khoury, Hanna J. ^[1]; Khuri, Fadlo R. ^[1]; Lee, Benjamin H. ^[7]; Ye, Keqiang ^[1]; Boggon, Titus J. ^[8]; Kang, Sumin ^[1]; He, Chuan ^[2]; Chen, Jing ^[1]

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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)

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

Related Subjects

59 BASIC BIOLOGICAL SCIENCES