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Phosphoglycerate Mutase 1 Coordinates Glycolysis and Biosynthesis to Promote Tumor Growth

Author(s): Hitosugi, Taro; Zhou, Lu; Elf, Shannon; Fan, Jun; Kang, Hee-Bum; et al

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Abstract: It remains unclear how cancer cells coordinate glycolysis and biosynthesis to support rapidly growing tumors. We found that 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 Date: Nov-2012
Citation: Hitosugi, Taro, Zhou, Lu, Elf, Shannon, Fan, Jun, Kang, Hee-Bum, Seo, Jae Ho, Shan, Changliang, Dai, Qing, Zhang, Liang, Xie, Jianxin, Gu, Ting-Lei, Jin, Peng, Alečković, Masa, LeRoy, Gary, Kang, Yibin, Sudderth, Jessica A, DeBerardinis, Ralph J, Luan, Chi-Hao, Chen, Georgia Z, Muller, Susan, Shin, Dong M, Owonikoko, Taofeek K, Lonial, Sagar, Arellano, Martha L, Khoury, Hanna J, Khuri, Fadlo R, Lee, Benjamin H, Ye, Keqiang, Boggon, Titus J, Kang, Sumin, He, Chuan, Chen, Jing. (2012). Phosphoglycerate Mutase 1 Coordinates Glycolysis and Biosynthesis to Promote Tumor Growth. Cancer Cell, 22 (5), 585 - 600. doi:10.1016/j.ccr.2012.09.020
DOI: doi:10.1016/j.ccr.2012.09.020
ISSN: 1535-6108
Pages: 1 - 27
Type of Material: Journal Article
Journal/Proceeding Title: Cancer Cell
Version: Author's manuscript

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