Evidence map›Paper›PMID 30970252›Full record

ArticleCell reports2019

Uncovering the Role of N-Acetyl-Aspartyl-Glutamate as a Glutamate Reservoir in Cancer.

Tu Nguyen, Brian James Kirsch, Ryoichi Asaka, Karim Nabi, Addison Quinones, Jessica Tan, Marjorie Justine Antonio, Felipe Camelo, Ting Li, Stephanie Nguyen and 17 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed
4.7field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

75 citing papers in PubMed, 102 citations in OpenAlex.

  1. Trial
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  3. Metabolic phenotypes of doxorubicin-induced cardiotoxicity among patients with breast cancer.Metabolomics : Official journal of the Metabolomic Society · 2026
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15 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

27 authors at 2 institutions in 3 countries.

Tu NguyenDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Brian James KirschDepartment 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.
Ryoichi AsakaDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Karim NabiDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Addison QuinonesDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Jessica TanDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Marjorie Justine AntonioDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Felipe CameloDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Ting LiDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Stephanie NguyenDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Giang HoangDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Kiet NguyenDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Sunag UdupaDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Christos SazeidesDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Yao-An ShenDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Amira ElgogaryDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Juvenal ReyesDepartment of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Liang ZhaoCenter for Alternatives to Animal Testing, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Andre KleensangCenter for Alternatives to Animal Testing, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Kaisorn Lee ChaichanaDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Thomas HartungCenter for Alternatives to Animal Testing, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA; University of Konstanz, 78464 Konstanz, Germany.
Michael J BetenbaughDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD 21218, USA.
Suely K MarieDepartment of Neurology, School of Medicine, University of São Paulo, São Paulo, Brazil.
Jin G JungDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Tian-Li WangDepartment 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.
Edward GabrielsonDepartment 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.
Anne LeDepartment 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.
Johns Hopkins University · USUniversidade de São Paulo · BR

Funding

Institute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1M
Probing the Connections between Monosaccharide Analogs, Sialic Acid Metabolism, aR01CA112314 · NCI · JOHNS HOPKINS UNIVERSITY · PI YAREMA, KEVIN J · 2005 to 2022
$4.5M
Glutaminase Inhibitor Drug Discovery and Nanoparticle-Based Delivery for Pancreatic Cancer TherapyR01CA193895 · NCI · JOHNS HOPKINS UNIVERSITY · PI HANES, JUSTIN S., LE, ANNE · 2016 to 2020
$2.1M
Thermo-Scientific Q Exactive Plus Orbitrap LC-MS/MS SystemS10OD025226 · OD · JOHNS HOPKINS UNIVERSITY · PI LE, ANNE · 2018 to 2018
$562k
Acquisition of Sony Biotechnology iCyt Synergy SY3200 BSC Cell SorterS10OD016230 · OD · JOHNS HOPKINS UNIVERSITY · PI MCCAFFERY, J. MICHAEL · 2014 to 2014
$520k
NCATS NIH HHS UL1 TR001079NCI NIH HHS R01 CA112314NCI NIH HHS R01 CA193895NIH HHS S10 OD016230NIH HHS S10 OD025226
6 · The paper itself

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.

Indexed as

Glutamic AcidHumansNeoplasmsGlutamic AcidGCPIIglutamate carboxypeptidase IIglutamate deprivationglutamate reservoirglutaminase inhibitormetabolomicsNAAGN-acetyl-aspartyl-glutamatestable isotope resolved

Identifiers

PMID30970252
PMCPMC6472703
OpenAlexW2937040465

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.