| Structural highlights
Publication Abstract from PubMed
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.
Phosphoglycerate mutase 1 coordinates glycolysis and biosynthesis to promote tumor growth.,Hitosugi T, Zhou L, Elf S, Fan J, Kang HB, Seo JH, Shan C, Dai Q, Zhang L, Xie J, Gu TL, Jin P, Aleckovic M, Leroy G, Kang Y, Sudderth JA, Deberardinis RJ, Luan CH, Chen GZ, Muller S, Shin DM, Owonikoko TK, Lonial S, Arellano ML, Khoury HJ, Khuri FR, Lee BH, Ye K, Boggon TJ, Kang S, He C, Chen J Cancer Cell. 2012 Nov 13;22(5):585-600. doi: 10.1016/j.ccr.2012.09.020. PMID:23153533[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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References
- ↑ Hitosugi T, Zhou L, Elf S, Fan J, Kang HB, Seo JH, Shan C, Dai Q, Zhang L, Xie J, Gu TL, Jin P, Aleckovic M, Leroy G, Kang Y, Sudderth JA, Deberardinis RJ, Luan CH, Chen GZ, Muller S, Shin DM, Owonikoko TK, Lonial S, Arellano ML, Khoury HJ, Khuri FR, Lee BH, Ye K, Boggon TJ, Kang S, He C, Chen J. Phosphoglycerate mutase 1 coordinates glycolysis and biosynthesis to promote tumor growth. Cancer Cell. 2012 Nov 13;22(5):585-600. doi: 10.1016/j.ccr.2012.09.020. PMID:23153533 doi:http://dx.doi.org/10.1016/j.ccr.2012.09.020
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