ArticleNature2016
Fumarate is an epigenetic modifier that elicits epithelial-to-mesenchymal transition.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 368 papers.
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.
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Who cites it
368 citing papers in PubMed, 568 citations in OpenAlex.
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- Metabolites with a message: impacts on epigenetics and implications for epimetabopathies.EMBO reports · 2026Review
- HIRA loss is frequent but not universal in human fumarate hydratase-deficient renal cell carcinoma and defines divergent oncogenic programs.Biomarker research · 2026Article
- Epithelial-mesenchymal transition in carcinoma: navigating phenotypic states to target resistance and metastasis.Cancer metastasis reviews · 2026Review
- Crosstalk between S-nitrosylation and glycation defines a metabolic vulnerability in liver and renal cancers.Nature communications · 2026Article
- Metabolic Bottlenecks and Opportunities: Reshaping the Tumor Microenvironment for Cancer Immunotherapy.Cells · 2026Review
- Endogenous metabolite signaling orchestrates tumor immune evasion.Cell insight · 2026Review
- Expansion of Germline Variants in Primary Hyperparathyroidism: Fumarate Hydratase Deficiency as a Cause of Parathyroid Adenomas.Endocrine pathology · 2026Observational
- Absolute quantitative proteomics guides patient-stratified drug repurposing in clear cell and papillary renal cell carcinoma.bioRxiv : the preprint server for biology · 2026Article
- Tumoral Metabolism at the Intersection of Oncogene Signaling, Epigenetics and Immunology: Emerging Therapeutic Strategies in Cancer.Current issues in molecular biology · 2026Review
- Reprogramming of valine metabolism mediated by abnormally low ALDH6A1 expression promotes invasive metastasis of gastric cancer.Science advances · 2026Article
- Glutamate accumulation in myelofibrosis microenvironment rewires mesenchymal stromal cells metabolic and epigenetic profiles.Cell communication and signaling : CCS · 2026Article
- Lactate-induced H3K4me3 histone mark promotes PLOD1-driven prostate cancer invasion.Cell death & disease · 2026Article
- Impact of mitochondrial reductive stress due to respiratory chain limitation on cancer via posttranslational modifications.Redox biology · 2026Review
- PHD1-dependent hydroxylation of RepoMan (CDCA2) on P604 modulates the control of mitotic progression.eLife · 2026Article
- Review
308 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
24 authors at 7 institutions in 2 countries.
Funding
Abstract
Mutations of the tricarboxylic acid cycle enzyme fumarate hydratase cause hereditary leiomyomatosis and renal cell cancer. Fumarate hydratase-deficient renal cancers are highly aggressive and metastasize even when small, leading to a very poor clinical outcome. Fumarate, a small molecule metabolite that accumulates in fumarate hydratase-deficient cells, plays a key role in cell transformation, making it a bona fide oncometabolite. Fumarate has been shown to inhibit α-ketoglutarate-dependent dioxygenases that are involved in DNA and histone demethylation. However, the link between fumarate accumulation, epigenetic changes, and tumorigenesis is unclear. Here we show that loss of fumarate hydratase and the subsequent accumulation of fumarate in mouse and human cells elicits an epithelial-to-mesenchymal-transition (EMT), a phenotypic switch associated with cancer initiation, invasion, and metastasis. We demonstrate that fumarate inhibits Tet-mediated demethylation of a regulatory region of the antimetastatic miRNA cluster mir-200ba429, leading to the expression of EMT-related transcription factors and enhanced migratory properties. These epigenetic and phenotypic changes are recapitulated by the incubation of fumarate hydratase-proficient cells with cell-permeable fumarate. Loss of fumarate hydratase is associated with suppression of miR-200 and the EMT signature in renal cancer and is associated with poor clinical outcome. These results imply that loss of fumarate hydratase and fumarate accumulation contribute to the aggressive features of fumarate hydratase-deficient tumours.
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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.