ArticlePloS one2014
A fluorescence-coupled assay for gamma aminobutyric acid (GABA) reveals metabolic stress-induced modulation of GABA content in neuroendocrine cancer.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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.
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Who cites it
20 citing papers in PubMed, 47 citations in OpenAlex.
- Discovery of Plant-Derived Natural Compounds as Novel GABA Aminotransferase Inhibitors: Structure-Based Discovery, Experimental Validation, and Molecular Dynamics Analysis.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Neural Circuits between Nodose Ganglion and Pulmonary Neuroendocrine Cells Regulate Lung Inflammatory Responses.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Are HDAC and Glutamine Synthetase Expression Levels Associated with Ga68-DOTATATE PET/CT Data and Prognosis in Gastroenteropancreatic Neuroendocrine Tumours?Medicina (Kaunas, Lithuania) · 2025Article
- Article
- Integrated analysis identifies GABRB3 as a biomarker in prostate cancer.BMC medical genomics · 2024Article
- Discovery of GABA Aminotransferase Inhibitors via Molecular Docking, Molecular Dynamic Simulation, and Biological Evaluation.International journal of molecular sciences · 2023Article
- GAD1 contributes to the progression and drug resistance in castration resistant prostate cancer.Cancer cell international · 2023Article
- The Long Noncoding RNA Cytoskeleton Regulator RNA (CYTOR)/miRNA-24-3p Axis Facilitates Nasopharyngeal Carcinoma Progression by Modulating GAD1 Expression.Journal of oncology · 2023Article
- A GC-MS-based untargeted metabolomics approach for comprehensive metabolic profiling of vancomycin-induced toxicity in mice.Heliyon · 2022Article
- Review
- Article
- The Metabolic Interplay between Cancer and Other Diseases.Trends in cancer · 2019Review
- Spatiotemporal pH Heterogeneity as a Promoter of Cancer Progression and Therapeutic Resistance.Cancers · 2019Review
- Uterine fluid proteome changes during diapause and resumption of embryo development in roe deer (Capreolus capreolus).Reproduction (Cambridge, England) · 2019Article
- γ-Aminobutyric acid inhibits the proliferation and increases oxaliplatin sensitivity in human colon cancer cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Avoiding Fluorescence Assay Interference-The Case for Diaphorase.Assay and drug development technologies · 2016Review
- Glutamate Decarboxylase 1 Overexpression as a Poor Prognostic Factor in Patients with Nasopharyngeal Carcinoma.Journal of Cancer · 2016Article
- Article
- An update of the classical and novel methods used for measuring fast neurotransmitters during normal and brain altered function.Current neuropharmacology · 2014Article
- Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Pathways involved in the synthesis of the neurotransmitter gamma-aminobutyric acid (GABA) have been implicated in the pathogenesis of high grade neuroendocrine (NE) neoplasms as well as neoplasms from a non-NE lineage. Using The Cancer Genome Atlas, overexpression of the GABA synthetic enzyme, glutamate decarboxylase 1 (GAD1), was found to be associated with decreased disease free-survival in prostate adenocarcinoma and decreased overall survival in clear cell renal cell carcinomas. Furthermore, GAD1 was found to be expressed in castrate-resistant prostate cancer cell lines, but not androgen-responsive cell lines. Using a novel fluorescence-coupled enzymatic microplate assay for GABA mediated through reduction of resazurin in a prostate neuroendocrine carcinoma (PNEC) cell line, acid microenvironment-induced stress increased GABA levels while alkaline microenvironment-induced stress decreased GABA through modulation of GAD1 and glutamine synthetase (GLUL) activities. Moreover, glutamine but not glucose deprivation decreased GABA through modulation of GLUL. Consistent with evidence in prokaryotic and eukaryotic organisms that GABA synthesis mediated through GAD1 may play a crucial role in surviving stress, GABA may be an important mediator of stress survival in neoplasms. These findings identify GABA synthesis and metabolism as a potentially important pathway for regulating cancer cell stress response as well as a potential target for therapeutic strategies.
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Registered trials
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.