ArticleOncotarget2014
Glutaminase 2 negatively regulates the PI3K/AKT signaling and shows tumor suppression activity in human hepatocellular carcinoma.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
What it found
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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.
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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
67 citing papers in PubMed, 93 citations in OpenAlex.
- Glutamine Metabolism in Health and Diseases.MedComm · 2026Review
- Decoding amino acid metabolism in hepatocellular carcinoma: critical nodes and novel therapeutic strategy.Frontiers in oncology · 2026Review
- Glutaminase Reprogramming in Hepatocellular Carcinoma: Implications for Diagnosis, Prognosis, and Potential as a Novel Therapeutic Target.International journal of molecular sciences · 2025Article
- Unveiling Metabolic Signatures as Potential Biomarkers in Common Cancers: Insights from Lung, Breast, Colorectal, Liver, and Gastric Tumours.Biomolecules · 2025Review
- UPLC-MS/MS Metabolomics Reveals Babao Dan's Mechanisms in MASH Treatment with Integrating Network Pharmacology and Molecular Docking.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Aging-associated mechanisms and metabolic vulnerabilities in esophageal carcinoma: an integrative review.Frontiers in cell and developmental biology · 2025Review
- Metabolic reprogramming in hepatocellular carcinoma: mechanisms of immune evasion and therapeutic implications.Frontiers in immunology · 2025Review
- Metabolic reprogramming and immunological changes in the microenvironment of esophageal cancer: future directions and prospects.Frontiers in immunology · 2025Review
- Glutaminase inhibition as potential cancer therapeutics: current status and future applications.Journal of enzyme inhibition and medicinal chemistry · 2024Review
- GLS2 reduces the occurrence of epilepsy by affecting mitophagy function in mouse hippocampal neurons.CNS neuroscience & therapeutics · 2024Article
- CD87-targeted BiTE and CAR-T cells potently inhibit invasive nonfunctional pituitary adenomas.Science China. Life sciences · 2024Article
- Targeting amino acid-metabolizing enzymes for cancer immunotherapy.Frontiers in immunology · 2024Review
- Glutaminase - A potential target for cancer treatment.BioMedicine · 2024Review
- Ferroptosis in hepatocellular carcinoma, from mechanism to effect.Frontiers in oncology · 2024Review
- Exploiting the Achilles' heel of cancer: disrupting glutamine metabolism for effective cancer treatment.Frontiers in pharmacology · 2024Review
- Review
- Two Faces of Glutaminase GLS2 in Carcinogenesis.Cancers · 2023Review
- Review
- Targeting Glutamine Metabolism as an Attractive Therapeutic Strategy for Acute Myeloid Leukemia.Current treatment options in oncology · 2023Review
- Small molecule inhibitors for cancer metabolism: promising prospects to be explored.Journal of cancer research and clinical oncology · 2023Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The tumor suppressor p53 and its signaling pathway play a critical role in tumor prevention. As a direct p53 target gene, the role of glutaminase 2 (GLS2) in tumorigenesis is unclear. In this study, we found that GLS2 expression is significantly decreased in majority of human hepatocellular carcinoma (HCC). Restoration of GLS2 expression in HCC cells inhibits the anchorage-independent growth of cells and reduces the growth of HCC xenograft tumors. Interestingly, we found that GLS2 negatively regulates the PI3K/AKT signaling, which is frequently activated in HCC. Blocking the PI3K/AKT signaling in HCC cells largely abolishes the inhibitory effect of GLS2 on the anchorage-independent cell growth and xenograft tumor growth. The GLS2 promoter is hypermethylated in majority of HCC samples. CpG methylation of GLS2 promoter inhibits GLS2 transcription, whereas reducing the methylation of GLS2 promoter induces GLS2 expression. Taken together, our results demonstrate that GLS2 plays an important role in tumor suppression in HCC, and the negative regulation of PI3K/AKT signaling contributes greatly to this function of GLS2. Furthermore, hypermethylation of GLS2 promoter is an important mechanism contributing to the decreased GLS2 expression in HCC.
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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.