ArticleThe Journal of clinical investigation2012
Epoxyeicosanoids stimulate multiorgan metastasis and tumor dormancy escape in mice.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 180 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
180 citing papers in PubMed, 289 citations in OpenAlex.
- Soluble epoxide hydrolase activity and pharmacologic inhibition in horses with chronic severe laminitis.Equine veterinary journal · 2017Trial
- Pharmacokinetics, pharmacodynamics and adverse event profile of GSK2256294, a novel soluble epoxide hydrolase inhibitor.British journal of clinical pharmacology · 2016Trial
- Dietary omega-3 fatty acids modulate the eicosanoid profile in man primarily via the CYP-epoxygenase pathway.Journal of lipid research · 2014Trial
- The Roles of EETs in Neurological Disorders.CNS neuroscience & therapeutics · 2026Review
- Crocetin Halts Tumorigenesis in Metastatic Breast Cancer via Disrupting CYP2J2/EET Axis.ACS omega · 2026Article
- Investigation of Thymoquinone as an Inhibitor of CYP2C8/EET Axis.Chembiochem : a European journal of chemical biology · 2026Article
- Targeting tumor dormancy: the next frontier in gastrointestinal stromal tumor therapy.Neoplasia (New York, N.Y.) · 2026Review
- Epoxide Hydrolase Family: Biological Functions, Disease Mechanisms, and Emerging Therapeutic Strategies.Biology · 2026Review
- Targeting dormant cancer cells: ferroptosis as a precision therapeutic strategy.Cellular & molecular biology letters · 2026Review
- Self-Immolative Systems in Diagnostic and Therapeutic Applications.ChemMedChem · 2026Review
- Liquid Chromatography-Tandem Mass Spectrometry-Based Targeted Lipidomic Analysis of Obesity-Related Colorectal Cancer: Potential Roles of the CYP Eicosanoid Pathway.The Journal of nutrition · 2026Article
- Targeting Lipid Metabolic Reprogramming to Overcome Immunotherapy Resistance: Systemic Nutritional Modulation and Precision Nanomedicine.International journal of nanomedicine · 2026Review
- Metabolic adaptations in cancer progression.Physiological reviews · 2026Review
- Integrated bioinformatics to identify and validate the role of oxidative stress-related gene EPHX2 in laryngeal cancer.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2026Article
- Regulation of P450-derived epoxy fatty acids in cardiovascular diseases.Redox biochemistry and chemistry · 2025Article
- Cytochrome P450-derived Epoxyeicosatrienoic Acid, the Regulation of Cardiovascular-related Diseases, and the Implication for Pulmonary Hypertension.Cardiovascular drugs and therapy · 2025Review
- The Hunt for the Putative Epoxyeicosatrienoic Acid Receptor.ACS chemical biology · 2025Review
- Metabolic landscape of disseminated cancer dormancy.Trends in cancer · 2025Review
- Cancer-associated fibroblasts in carcinogenesis.Journal of translational medicine · 2025Review
- EPHX2 overexpression deters the advancement of clear cell renal cell carcinoma via lipid metabolism reprogramming.Frontiers in oncology · 2025Article
120 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
31 authors at 9 institutions in 4 countries.
Funding
Abstract
Epoxyeicosatrienoic acids (EETs) are small molecules produced by cytochrome P450 epoxygenases. They are lipid mediators that act as autocrine or paracrine factors to regulate inflammation and vascular tone. As a result, drugs that raise EET levels are in clinical trials for the treatment of hypertension and many other diseases. However, despite their pleiotropic effects on cells, little is known about the role of these epoxyeicosanoids in cancer. Here, using genetic and pharmacological manipulation of endogenous EET levels, we demonstrate that EETs are critical for primary tumor growth and metastasis in a variety of mouse models of cancer. Remarkably, we found that EETs stimulated extensive multiorgan metastasis and escape from tumor dormancy in several tumor models. This systemic metastasis was not caused by excessive primary tumor growth but depended on endothelium-derived EETs at the site of metastasis. Administration of synthetic EETs recapitulated these results, while EET antagonists suppressed tumor growth and metastasis, demonstrating in vivo that pharmacological modulation of EETs can affect cancer growth. Furthermore, inhibitors of soluble epoxide hydrolase (sEH), the enzyme that metabolizes EETs, elevated endogenous EET levels and promoted primary tumor growth and metastasis. Thus, our data indicate a central role for EETs in tumorigenesis, offering a mechanistic link between lipid signaling and cancer and emphasizing the critical importance of considering possible effects of EET-modulating drugs on cancer.
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.