Phosphoglycerate Mutase 1 Coordinates Glycolysis and Biosynthesis to Promote Tumor Growth

Taro 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 MullerDong 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

Research output: Contribution to journalArticle

194 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)585-600
Number of pages16
JournalCancer cell
Volume22
Issue number5
DOIs
StatePublished - Nov 13 2012

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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  • Cite this

    Hitosugi, T., Zhou, L., Elf, S., Fan, J., Kang, H. B., Seo, J. H., Shan, C., Dai, Q., Zhang, L., Xie, J., Gu, T. L., Jin, P., Alečković, M., LeRoy, G., Kang, Y., Sudderth, J. A., DeBerardinis, R. J., Luan, C. H., Chen, G. Z., ... Chen, J. (2012). Phosphoglycerate Mutase 1 Coordinates Glycolysis and Biosynthesis to Promote Tumor Growth. Cancer cell, 22(5), 585-600. https://doi.org/10.1016/j.ccr.2012.09.020