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.
authors.affiliation: Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Taro
authors.initials: T
authors.lastname: Hitosugi
authors.forename: Lu
authors.initials: L
authors.lastname: Zhou
authors.forename: Shannon
authors.initials: S
authors.lastname: Elf
authors.forename: Jun
authors.initials: J
authors.lastname: Fan
authors.forename: Hee-Bum
authors.initials: HB
authors.lastname: Kang
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Seo
authors.forename: Changliang
authors.initials: C
authors.lastname: Shan
authors.forename: Qing
authors.initials: Q
authors.lastname: Dai
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.forename: Jianxin
authors.initials: J
authors.lastname: Xie
authors.forename: Ting-Lei
authors.initials: TL
authors.lastname: Gu
authors.forename: Peng
authors.initials: P
authors.lastname: Jin
authors.forename: Masa
authors.initials: M
authors.lastname: Alečković
authors.forename: Gary
authors.initials: G
authors.lastname: LeRoy
authors.forename: Yibin
authors.initials: Y
authors.lastname: Kang
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Sudderth
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: DeBerardinis
authors.forename: Chi-Hao
authors.initials: CH
authors.lastname: Luan
authors.forename: Georgia Z
authors.initials: GZ
authors.lastname: Chen
authors.forename: Susan
authors.initials: S
authors.lastname: Muller
authors.forename: Dong M
authors.initials: DM
authors.lastname: Shin
authors.forename: Taofeek K
authors.initials: TK
authors.lastname: Owonikoko
authors.forename: Sagar
authors.initials: S
authors.lastname: Lonial
authors.forename: Martha L
authors.initials: ML
authors.lastname: Arellano
authors.forename: Hanna J
authors.initials: HJ
authors.lastname: Khoury
authors.forename: Fadlo R
authors.initials: FR
authors.lastname: Khuri
authors.forename: Benjamin H
authors.initials: BH
authors.lastname: Lee
authors.forename: Keqiang
authors.initials: K
authors.lastname: Ye
authors.forename: Titus J
authors.initials: TJ
authors.lastname: Boggon
authors.forename: Sumin
authors.initials: S
authors.lastname: Kang
authors.forename: Chuan
authors.initials: C
authors.lastname: He
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004789:Enzyme Activation; D055785:Gene Knockdown Techniques; D005942:Gluconates / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005988:Glyceric Acids / Q000378:metabolism; D006019:Glycolysis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008958:Models, Molecular; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology; D010736:Phosphoglycerate Mutase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D005942:Gluconates; D005988:Glyceric Acids; C008885:2-phosphoglycerate; C005156:3-phosphoglycerate; D005954:Glucosephosphate Dehydrogenase; D010736:Phosphoglycerate Mutase; C008884:6-phosphogluconic acid