Oncotarget

Research Papers:

Hypotaurine evokes a malignant phenotype in glioma through aberrant hypoxic signaling

Peng Gao, Chunzhang Yang, Cody L. Nesvick, Michael J. Feldman, Saman Sizdahkhani, Huailei Liu, Huiying Chu, Fengxu Yang, Ling Tang, Jing Tian, Shiguang Zhao, Guohui Li, John D. Heiss, Yang Liu, Zhengping Zhuang _ and Guowang Xu

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2016; 7:15200-15214. https://doi.org/10.18632/oncotarget.7710

Metrics: PDF 2985 views  |   HTML 3376 views  |   ?  


Abstract

Peng Gao1,6,*, Chunzhang Yang2,7,*, Cody L. Nesvick2, Michael J. Feldman2, Saman Sizdahkhani2, Huailei Liu3, Huiying Chu4, Fengxu Yang1,5, Ling Tang1, Jing Tian5, Shiguang Zhao3, Guohui Li4, John D. Heiss2, Yang Liu1, Zhengping Zhuang2, Guowang Xu1

1Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China

2Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA

3Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China

4Laboratory of Molecular Modeling and Design, State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Science, Dalian, China

5School of Bioengineering, Dalian Polytechnic University, Dalian, China

6Clinical Laboratory, Dalian Sixth People’s Hospital, Dalian, China

7Neuro-Oncology Branch, National Cancer Institute, NIH, Bethesda, MD, USA

*These authors have contributed equally to this work

Correspondence to:

Zhengping Zhuang, e-mail: [email protected]

Guowang Xu, e-mail: [email protected]

Shiguang Zhao, e-mail: [email protected]

Guohui Li, e-mail: [email protected]

Keywords: hypoxia, hypoxia-inducible factors, hypotaurine, metabolomics, glioma

Received: November 17, 2015    Accepted: January 31, 2016    Published: February 25, 2016

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 7710