ArticleNature cell biology2016
Regional glutamine deficiency in tumours promotes dedifferentiation through inhibition of histone demethylation.
Article in Nature cell biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 255 papers, 1 of them a synthesis that pooled it.
What it found
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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
255 citing papers in PubMed, 1 synthesis or guideline pooled it, 364 citations in OpenAlex.
- Tumour-Associated Neutrophils in Colorectal Cancer: a Systematic Review, Meta-analysis, and Comprehensive Literature Review.Journal of gastrointestinal cancer · 2026Pooled it
- Enhanced SIRT3 activity potentiates germinal center epigenetic modulation through α-ketoglutarate.The Journal of biological chemistry · 2026Article
- Illuminating spatial dynamics of glutamine metabolism with a sensitive genetically encoded biosensor.RSC chemical biology · 2026Article
- L-Glutamine in combination with first-line gemcitabine and nab-paclitaxel in advanced pancreatic ductal adenocarcinoma: an open-label, single-arm, phase 1 GlutaPanc trial.Nature cancer · 2026Article
- Glucose and Glutamine Deprivation Promotes Breast Cancer Lung Metastasis via BRD4-Dependent Enhancer Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Glutamine stress promotes metastatic potential via hexosamine biosynthetic pathway activity in KRAS/STK11-mutant lung adenocarcinoma.Research square · 2026Article
- Unraveling the role of glutamine metabolism in cancer: from cell death mechanisms to tumor microenvironment modulation.Experimental hematology & oncology · 2026Review
- ACSS2 is required for colorectal cancer progression and a druggable target for colorectal cancer treatment.iScience · 2026Article
- Sijunzi Decoction Reverses Metabolic Adaptation and Induces Ferroptosis in Cisplatin-Resistant Non-small Cell Lung Cancer: An Integrative Metabolomics-Pharmacology Analysis.Current medical science · 2026Article
- TP53 mutations in triple-negative breast cancer cells confer sensitivity to ASCT2 inhibition via arginine uptake.Cell death & disease · 2026Article
- The crosstalk between epigenetics and metabolism in the malignant cell.Discover oncology · 2026Review
- Mitochondrial uncoupling inhibits serine catabolismCancer biology & medicine · 2026Article
- α-Ketoglutarate protects against cartilage damage via epigenetically driven metabolic reprogramming in osteoarthritis models.The Journal of clinical investigation · 2026Article
- A phenotype-based cell culture model of melanoma cells that persist as residual disease after therapies leading to recurrence.Research square · 2026Article
- WTAP-Mediated Glutaminase Splicing Bias Suppresses Ferroptosis in Hepatocellular Carcinoma.Cancer communications (London, England) · 2026Article
- Epigenetic crosstalk in neuroblastoma development and progression.Frontiers in cell and developmental biology · 2026Review
- Review
- Targeting cell surface GRP78-CD44v interaction suppresses cell migration in triple-negative breast cancer cells.Scientific reports · 2025Article
- Article
- Lysine demethylases 6 A and 6B as epigenetic regulators in therapeutic resistance of cancer.Clinical epigenetics · 2025Review
195 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
19 authors at 5 institutions in 1 country.
Funding
Abstract
Poorly organized tumour vasculature often results in areas of limited nutrient supply and hypoxia. Despite our understanding of solid tumour responses to hypoxia, how nutrient deprivation regionally affects tumour growth and therapeutic response is poorly understood. Here, we show that the core region of solid tumours displayed glutamine deficiency compared with other amino acids. Low glutamine in tumour core regions led to dramatic histone hypermethylation due to decreased α-ketoglutarate levels, a key cofactor for the Jumonji-domain-containing histone demethylases. Using patient-derived (V600E)BRAF melanoma cells, we found that low-glutamine-induced histone hypermethylation resulted in cancer cell dedifferentiation and resistance to BRAF inhibitor treatment, which was largely mediated by methylation on H3K27, as knockdown of the H3K27-specific demethylase KDM6B and the methyltransferase EZH2 respectively reproduced and attenuated the low-glutamine effects in vitro and in vivo. Thus, intratumoral regional variation in the nutritional microenvironment contributes to tumour heterogeneity and therapeutic response.
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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.