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Uncovering the Role of N-Acetyl-Aspartyl-Glutamate as a Glutamate Reservoir in Cancer.
Nguyen, Tu; Kirsch, Brian James; Asaka, Ryoichi; Nabi, Karim; Quinones, Addison; Tan, Jessica; Antonio, Marjorie Justine; Camelo, Felipe; Li, Ting; Nguyen, Stephanie; Hoang, Giang; Nguyen, Kiet; Udupa, Sunag; Sazeides, Christos; Shen, Yao-An; Elgogary, Amira; Reyes, Juvenal; Zhao, Liang; Kleensang, Andre; Chaichana, Kaisorn Lee; Hartung, Thomas; Betenbaugh, Michael J; Marie, Suely K; Jung, Jin G; Wang, Tian-Li; Gabrielson, Edward; Le, Anne.
Affiliation
  • Nguyen T; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Kirsch BJ; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD 21218, USA.
  • Asaka R; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Nabi K; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Quinones A; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Tan J; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Antonio MJ; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Camelo F; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Li T; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Nguyen S; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Hoang G; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Nguyen K; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Udupa S; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Sazeides C; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Shen YA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Elgogary A; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Reyes J; Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Zhao L; Center for Alternatives to Animal Testing, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
  • Kleensang A; Center for Alternatives to Animal Testing, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
  • Chaichana KL; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Hartung T; Center for Alternatives to Animal Testing, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA; University of Konstanz, 78464 Konstanz, Germany.
  • Betenbaugh MJ; Department of Chemical and Biomolecular Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD 21218, USA.
  • Marie SK; Department of Neurology, School of Medicine, University of São Paulo, São Paulo, Brazil.
  • Jung JG; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Wang TL; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Gabrielson E; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Le A; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: annele@jhmi.edu.
Cell Rep ; 27(2): 491-501.e6, 2019 04 09.
Article de En | MEDLINE | ID: mdl-30970252
ABSTRACT
N-acetyl-aspartyl-glutamate (NAAG) is a peptide-based neurotransmitter that has been extensively studied in many neurological diseases. In this study, we show a specific role of NAAG in cancer. We found that NAAG is more abundant in higher grade cancers and is a source of glutamate in cancers expressing glutamate carboxypeptidase II (GCPII), the enzyme that hydrolyzes NAAG to glutamate and N-acetyl-aspartate (NAA). Knocking down GCPII expression through genetic alteration or pharmacological inhibition of GCPII results in a reduction of both glutamate concentrations and cancer growth. Moreover, targeting GCPII in combination with glutaminase inhibition accentuates these effects. These findings suggest that NAAG serves as an important reservoir to provide glutamate to cancer cells through GCPII when glutamate production from other sources is limited. Thus, GCPII is a viable target for cancer therapy, either alone or in combination with glutaminase inhibition.
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Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Acide glutamique / Tumeurs Limites: Humans Langue: En Journal: Cell Rep Année: 2019 Type de document: Article Pays d'affiliation: États-Unis d'Amérique
Texte intégral
Ajouter à My VHL
Imprimer
XML
PubMed Links
Recherche sur Google

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Acide glutamique / Tumeurs Limites: Humans Langue: En Journal: Cell Rep Année: 2019 Type de document: Article Pays d'affiliation: États-Unis d'Amérique