ArticleNeoplasia (New York, N.Y.)2020
Glutamine deprivation counteracts hypoxia-induced chemoresistance.
Article in Neoplasia (New York, N.Y.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Inhibition of Glutamate Dehydrogenase as a Potential Strategy to Modulate Intrahepatic Cholangiocarcinoma Cell Metabolism.Biomolecules · 2026Article
- Amino acid metabolic reprogramming: future prospects for cholangiocarcinoma therapy.Cell death discovery · 2026Review
- Cholangiocarcinoma 2026: status quo, unmet needs and priorities.Nature reviews. Gastroenterology & hepatology · 2026Review
- mTOR signaling in cholangiocarcinoma: mechanistic insights and therapeutic opportunities.Frontiers in pharmacology · 2026Review
- Glutamine synthetase shields triple-negative breast cancer cells from ferroptosis in metastasis triggered by glutamine deprivation.Breast cancer research : BCR · 2025Article
- BCR::ABL1 expression in chronic myeloid leukemia cells in low oxygen is regulated by glutamine via CD36-mediated fatty acid uptake.Cancer cell international · 2025Article
- Demystifying metabolic‒immune crosstalk: how amino acid metabolic reprogramming shapes the malignant phenotype and macrophage polarization of biliary and pancreatic tumors.International journal of biological sciences · 2025Review
- Mass Spectrometry Imaging of Coniine and Other Hemlock Alkaloids after On-Tissue Derivatization Reveals Distinct Alkaloid Distributions in the Plant.Journal of natural products · 2024Article
- Overcoming Cancer Persister Cells by Stabilizing the ATF4 Promoter G-quadruplex.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Mass spectrometry imaging methods for visualizing tumor heterogeneity.Current opinion in biotechnology · 2024Review
- The role of metabolic reprogramming in liver cancer and its clinical perspectives.Frontiers in oncology · 2024Review
- Comparative analysis of bile metabolic profile in patients with biliary obstruction complicated byFrontiers in cellular and infection microbiology · 2023Article
- Identification of a glutamine metabolism reprogramming signature for predicting prognosis, immunotherapy efficacy, and drug candidates in bladder cancer.Frontiers in immunology · 2023Article
- An overview of extrahepatic cholangiocarcinoma: from here to where?Frontiers in oncology · 2023Review
- Glutamine stabilizes myc via alpha-ketoglutarate and regulates paclitaxel sensitivity.Medical oncology (Northwood, London, England) · 2022Article
- Glutamine Transporter SLC1A5 Regulates Ionizing Radiation-Derived Oxidative Damage and Ferroptosis.Oxidative medicine and cellular longevity · 2022Article
- Article
- Recent developments of novel matrices and on-tissue chemical derivatization reagents for MALDI-MSI.Analytical and bioanalytical chemistry · 2021Review
- Review
- Adipocytic Glutamine Synthetase UpregulationFrontiers in oncology · 2021Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The microenvironment of solid tumors is a key determinant of therapy efficacy. The co-occurrence of oxygen and nutrient deprivation is a common phenomenon of the tumor microenvironment and associated with treatment resistance. Cholangiocarcinoma (CCA) is characterized by a very poor prognosis and pronounced chemoresistance. A better understanding of the underlying molecular mechanisms is urgently needed to improve therapy strategies against CCA. We sought to investigate the importance of the conditionally essential amino acid glutamine, a centrally important nutrient for a variety of solid tumors, for CCA. Glutamine levels were strongly decreased in CCA samples and the growth of established human CCA cell lines was highly dependent on glutamine. Using gradual reduction of external glutamine, we generated derivatives of CCA cell lines which were able to grow without external glutamine (termed glutamine-depleted (GD)). To analyze the effects of coincident oxygen and glutamine deprivation, GD cells were treated with cisplatin or gemcitabine under normoxia and hypoxia. Strikingly, the well-established phenomenon of hypoxia-induced chemoresistance was completely reversed in GD cells. In order to better understand the underlying mechanisms, we focused on the oncogene c-Myc. The combination of cisplatin and hypoxia led to sustained c-Myc protein expression in wildtype cells. In contrast, c-Myc expression was reduced in response to the combinatorial treatment in GD cells, suggesting a functional importance of c-Myc in the process of hypoxia-induced chemoresistance. In summary, these findings indicate that the mechanisms driving adaption to tumor microenvironmental changes and their relevance for the response to therapy are more complex than expected.
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