ArticleOncotarget2015
Inhibition of glutamine metabolism counteracts pancreatic cancer stem cell features and sensitizes cells to radiotherapy.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
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.
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.
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Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.
- The metabolic addiction of cancer stem cells.Frontiers in oncology · 2022Pooled it
- Metabolism and Immunity-Adapted Radiotherapy (M.I.A.R): A Conceptual Framework for Overcoming the Therapeutic Plateau in Clinical Radiotherapy.Current oncology (Toronto, Ont.) · 2026Review
- The metabolic profiles of cancer stem cells.Stem cell research & therapy · 2026Review
- Dependency of Non-Small Cell Lung Cancer Cells on Glutamine and Glucose Levels in the Presence of Metformin.The Eurasian journal of medicine · 2026Article
- Regulation of Autophagy and Metabolism in Hepatocellular Carcinoma: Involvement of Wnt-β-Catenin Pathway.Journal of cellular and molecular medicine · 2026Article
- HDAC4 Promotes Cancer Stemness in Nonsmall Cell Lung Cancer by Upregulating SLC38A2 Expression via HIF-1α to Enhance Glutamine Metabolism.Analytical cellular pathology (Amsterdam) · 2026Article
- Metabolic reprogramming and plasticity of cancer stem cells.Frontiers in cell and developmental biology · 2026Review
- Redox-Amino Acid Metabolic Crosstalk in Ovarian Cancer Stem Cells: Integrating Metabolic Reprogramming, Signaling, and the Tumor Microenvironment.Antioxidants (Basel, Switzerland) · 2025Review
- Inhibition of glutamine synthetase enhances hepatocellular carcinoma radiosensitivity through ROS-induced excessive mitophagy.Molecular biology reports · 2025Article
- Review
- Review
- Metabolic Signaling in the Tumor Microenvironment.Cancers · 2025Review
- Emerging mechanisms and promising approaches in pancreatic cancer metabolism.Cell death & disease · 2024Review
- Long-acting Erwinia chrysanthemi, Pegcrisantaspase, induces alternate amino acid biosynthetic pathways in a preclinical model of pancreatic ductal adenocarcinoma.Cancer & metabolism · 2024Article
- Metabolic Profiles of Cancer Stem Cells and Normal Stem Cells and Their Therapeutic Significance.Cells · 2023Review
- Transcriptome and Lipidomic Analysis Suggests Lipid Metabolism Reprogramming and UpregulatingMetabolites · 2023Article
- Therapeutic Strategies for Pancreatic-Cancer-Related Type 2 Diabetes Centered around Natural Products.International journal of molecular sciences · 2023Review
- Article
- The role of tumor microenvironment on cancer stem cell fate in solid tumors.Cell communication and signaling : CCS · 2023Review
- Eradicating the tumor "seeds": nanomedicines-based therapies against cancer stem cells.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2023Review
2 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
15 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) cells utilize a novel non-canonical pathway of glutamine metabolism that is essential for tumor growth and redox balance. Inhibition of this metabolic pathway in PDAC can potentially synergize with therapies that increase intracellular reactive oxygen species (ROS) such as radiation. Here, we evaluated the dependence of pancreatic cancer stem cells (PCSCs) on this non-canonical glutamine metabolism pathway and researched whether inhibiting this pathway can enhance radiosensitivity of PCSCs. We showed that glutamine deprivation significantly inhibited self-renewal, decreased expression of stemness-related genes, increased intracellular ROS, and induced apoptosis in PCSCs. These effects were countered by oxaloacetate, but not α-ketoglutarate. Knockdown of glutamic-oxaloacetic transaminase dramatically impaired PCSCs properties, while glutamate dehydrogenase knockdown had a limited effect, suggesting a dependence of PCSCs on non-canonical glutamine metabolism. Additionally, glutamine deprivation significantly increased radiation-induced ROS and sensitized PCSCs to fractionated radiation. Moreover, transaminase inhibitors effectively enhanced ROS generation, promoted radiation sensitivity, and attenuated tumor growth in nude mice following radiation exposure. Our findings reveal that inhibiting the non-canonical pathway of glutamine metabolism enhances the PCSC radiosensitivity and may be an effective adjunct in cancer radiotherapy.
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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.