ReviewInternational journal of molecular sciences2021
Understanding the Central Role of Citrate in the Metabolism of Cancer Cells and Tumors: An Update.
Review in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
82 citing papers in PubMed, 125 citations in OpenAlex.
- Mitochondrial metabolite transporters at the crossroads of metabolic reprogramming, epigenetic regulation and therapeutic vulnerabilities in colorectal cancer.Molecular biology reports · 2026Review
- The Role of Anti-Inflammatory Nutrition in Metabolic Syndrome and Cardiometabolic Diseases.Nutrients · 2026Review
- Oncometabolites in Cancer Metabolism: Mechanistic Insights and Biomarker Potential- A Narrative Review.Health science reports · 2026Article
- A Role for Astrocyte Metabolism in Species-Specific Neuronal Development.bioRxiv : the preprint server for biology · 2026Article
- Review
- Metab8D: a metabolic regulome network from multiomics and machine learning.Communications biology · 2026Article
- Thermosensitive citrate-based mussel-inspired attack-defense integrated bioadhesives facilitate complicated wound healing.Bioactive materials · 2026Article
- Evaluation of in vitro toxicity of common phytochemicals included in weight loss supplements usingFEBS open bio · 2026Article
- Beyond the membrane: Internalization and compartmentalization of insulin‑like growth factor 1 receptor signaling in cancer pathogenesis and treatment (Review).International journal of oncology · 2026Review
- Absolute dynamic and relative static: the relationship of glycolysis and OXPHOS in cancer development.Cell death discovery · 2026Review
- Mixed Waste Streams for Bioproduction: Exploring Bacterial Wax Ester Production in Nitrogen-Rich Acidogenic Fermentate.Microbial biotechnology · 2026Article
- Metabolic Symbiosis Between Cancer Cells and Endothelial Cells: A Key Driver of Tumor Angiogenesis.Advances in experimental medicine and biology · 2026Review
- Beyond Bioenergetics: Emerging Roles of Mitochondrial Fatty Acid Oxidation in Stress Response and Aging.Cells · 2025Review
- Targeting mitochondrial transporters and metabolic reprogramming for disease treatment.Journal of translational medicine · 2025Review
- Bioactive Compounds, Antioxidant, Antimicrobial and Anticancerogenic Activity inAntioxidants (Basel, Switzerland) · 2025Article
- Mitochondrial bioenergetics and networks in melanoma: an update.Apoptosis : an international journal on programmed cell death · 2025Review
- Absolute quantification of TCA cycle intermediates in mouse ocular tissues reveals distinct tissue- and sex-specific mitochondrial metabolism.bioRxiv : the preprint server for biology · 2025Article
- Herbal Weight Loss Supplements Induce Metabolomic In Vitro Changes Indicative of Oxidative Stress.Metabolites · 2025Article
- Methods and Guidelines for Metabolism Studies: Applications to Cancer Research.International journal of molecular sciences · 2025Review
- Oxidative and Glycolytic Metabolism: Their Reciprocal Regulation and Dysregulation in Cancer.Cells · 2025Review
22 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
8 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Citrate plays a central role in cancer cells' metabolism and regulation. Derived from mitochondrial synthesis and/or carboxylation of α-ketoglutarate, it is cleaved by ATP-citrate lyase into acetyl-CoA and oxaloacetate. The rapid turnover of these molecules in proliferative cancer cells maintains a low-level of citrate, precluding its retro-inhibition on glycolytic enzymes. In cancer cells relying on glycolysis, this regulation helps sustain the Warburg effect. In those relying on an oxidative metabolism, fatty acid β-oxidation sustains a high production of citrate, which is still rapidly converted into acetyl-CoA and oxaloacetate, this latter molecule sustaining nucleotide synthesis and gluconeogenesis. Therefore, citrate levels are rarely high in cancer cells. Resistance of cancer cells to targeted therapies, such as tyrosine kinase inhibitors (TKIs), is frequently sustained by aerobic glycolysis and its key oncogenic drivers, such as Ras and its downstream effectors MAPK/ERK and PI3K/Akt. Remarkably, in preclinical cancer models, the administration of high doses of citrate showed various anti-cancer effects, such as the inhibition of glycolysis, the promotion of cytotoxic drugs sensibility and apoptosis, the neutralization of extracellular acidity, and the inhibition of tumors growth and of key signalling pathways (in particular, the IGF-1R/AKT pathway). Therefore, these preclinical results support the testing of the
Indexed as
Identifiers
What OpenQuestion holds
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.