@article{1d7bea82238a488583dfac8810a436db,
title = "Phosphoglycerate Mutase 1 Coordinates Glycolysis and Biosynthesis to Promote Tumor Growth",
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.",
author = "Taro Hitosugi and Lu Zhou and Shannon Elf and Jun Fan and Kang, {Hee Bum} and Seo, {Jae Ho} and Changliang Shan and Qing Dai and Liang Zhang and Jianxin Xie and Gu, {Ting Lei} and Peng Jin and Masa Ale{\v c}kovi{\'c} and Gary LeRoy and Yibin Kang and Sudderth, {Jessica A.} and DeBerardinis, {Ralph J.} and Luan, {Chi Hao} and Chen, {Georgia Z.} and Susan Muller and Shin, {Dong M.} and Owonikoko, {Taofeek K.} and Sagar Lonial and Arellano, {Martha L.} and Khoury, {Hanna J.} and Khuri, {Fadlo R.} and Lee, {Benjamin H.} and Keqiang Ye and Boggon, {Titus J.} and Sumin Kang and Chuan He and Jing Chen",
note = "Funding Information: We thank Susan Sunay at the Hematology Division Tissue Bank, Winship Cancer Institute of Emory, for providing primary tissue samples from patients with leukemia, Drs. Sagar Lonial and Lawrence Boise for providing peripheral blood samples from healthy donors, and Dr. Yoke Wah Kow for human HaCaT and PIG1 cell lines. This work was supported in part by NIH Grants CA120272 (to J.C.), CA140515 (to J.C.), GM071440 (to C.H.), and the Pharmacological Sciences Training Grant T32 GM008602 (to S.E.). J.X. and T.-L.G. are employees of Cell Signaling Technology, Inc. T.H. is a Fellow Scholar of the American Society of Hematology. S.E. is an NIH pre-doctoral fellow and an ARCS Foundation Scholar. G.Z.C., D.M.S., F.R.K., S.K., and J.C. are Georgia Cancer Coalition Distinguished Cancer Scholars. S.K. is a Robbins Scholar. S.K. and J.C. are American Cancer Society Basic Research Scholars. J.C. is a Scholar of the Leukemia and Lymphoma Society. ",
year = "2012",
month = nov,
day = "13",
doi = "10.1016/j.ccr.2012.09.020",
language = "English (US)",
volume = "22",
pages = "585--600",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "5",
}