title: Hypotaurine evokes a malignant phenotype in glioma through aberrant hypoxic signaling.
abstract: Metabolomics has shown significant potential in identifying small molecules specific to tumor phenotypes. In this study we analyzed resected tissue metabolites using capillary electrophoresis-mass spectrometry and found that tissue hypotaurine levels strongly and positively correlated with glioma grade. In vitro studies were conducted to show that hypotaurine activates hypoxia signaling through the competitive inhibition of prolyl hydroxylase domain-2. This leads to the activation of hypoxia signaling as well as to the enhancement of glioma cell proliferation and invasion. In contrast, taurine, the oxidation metabolite of hypotaurine, decreased intracellular hypotaurine and resulted in glioma cell growth arrest. Lastly, a glioblastoma xenograft mice model was supplemented with taurine feed and exhibited impaired tumor growth. Taken together, these findings suggest that hypotaurine is an aberrantly produced oncometabolite, mediating tumor molecular pathophysiology and progression. The hypotaurine metabolic pathway may provide a potentially new target for glioblastoma diagnosis and therapy.
authors.affiliation: Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.|Clinical Laboratory, Dalian Sixth People's Hospital, Dalian, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Gao
authors.affiliation: Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.|Neuro-Oncology Branch, National Cancer Institute, NIH, Bethesda, MD, USA.
authors.forename: Chunzhang
authors.initials: C
authors.lastname: Yang
authors.affiliation: Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Cody L
authors.initials: CL
authors.lastname: Nesvick
authors.affiliation: Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Feldman
authors.affiliation: Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Saman
authors.initials: S
authors.lastname: Sizdahkhani
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Huailei
authors.initials: H
authors.lastname: Liu
authors.affiliation: Laboratory of Molecular Modeling and Design, State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Science, Dalian, China.
authors.forename: Huiying
authors.initials: H
authors.lastname: Chu
authors.affiliation: Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.|School of Bioengineering, Dalian Polytechnic University, Dalian, China.
authors.forename: Fengxu
authors.initials: F
authors.lastname: Yang
authors.affiliation: Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Tang
authors.affiliation: School of Bioengineering, Dalian Polytechnic University, Dalian, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Tian
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Shiguang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Laboratory of Molecular Modeling and Design, State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Science, Dalian, China.
authors.forename: Guohui
authors.initials: G
authors.lastname: Li
authors.affiliation: Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Heiss
authors.affiliation: Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Zhuang
authors.affiliation: Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
authors.forename: Guowang
authors.initials: G
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D002453:Cell Cycle; D049109:Cell Proliferation; D005500:Follow-Up Studies; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D055432:Metabolomics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010641:Phenotype; D011379:Prognosis; D015398:Signal Transduction; D013654:Taurine / Q000031:analogs & derivatives* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D013654:Taurine; C003949:hypotaurine
keywords: glioma; hypotaurine; hypoxia; hypoxia-inducible factors; metabolomics