ArticleCancer & metabolism2013
Reversed argininosuccinate lyase activity in fumarate hydratase-deficient cancer cells.
Article in Cancer & metabolism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
What it found
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Who cites it
76 citing papers in PubMed, 103 citations in OpenAlex.
- Metabolic regulation of calcium homeostasis via SERCA succination.Science advances · 2026Article
- ASS1-derived argininosuccinate promotes purine nucleoside synthesis in B cell acute lymphoblastic leukaemia.Nature metabolism · 2026Article
- Vespakinin-M delineates an AMPK/mTOR-arginine-TCA cycle axis to act as an immunometabolic switch in post-stroke microglia.Redox biology · 2026Article
- Pegargiminase Suppresses the Fanconi Anemia Pathway and Promotes Melphalan-Induced DNA Double-Strand Breaks in Uveal Melanoma.Pigment cell & melanoma research · 2026Article
- Nitrogen Isotope Effects in Urea Metabolism: From Biochemistry toInternational journal of molecular sciences · 2026Review
- SPEND-hSRS imaging of fumarate uncovers mitochondrial metabolic heterogeneity.bioRxiv : the preprint server for biology · 2026Article
- Metabolic permissiveness: how tissue context shapes cancer.Genes & development · 2026Review
- Fumarate activates the IL-6/JAK/STAT3 pathway by inhibiting KDM4C-mediated H3K36me3 demethylation in FH-knockdown renal cancer cells.British journal of cancer · 2025Article
- Ceramide-Induced Metabolic Stress Depletes Fumarate and Drives Mitophagy to Mediate Tumor Suppression.Cancer research · 2025Article
- Arginine promotes the activation of human lung fibroblasts independent of its metabolism.The Biochemical journal · 2025Article
- ADSL-generated fumarate binds and inhibits STING to promote tumour immune evasion.Nature cell biology · 2025Article
- Knowledge-Based Therapeutics for Tricarboxylic Acid (TCA) Cycle-Deficient Cancers.Cold Spring Harbor perspectives in medicine · 2024Review
- Raman micro-spectroscopy reveals the spatial distribution of fumarate in cells and tissues.Nature communications · 2024Article
- Metabolic alterations in hereditary and sporadic renal cell carcinoma.Nature reviews. Nephrology · 2024Review
- Rewiring of RNA methylation by the oncometabolite fumarate in renal cell carcinoma.NAR cancer · 2024Article
- Fumarate induces LncRNA-MIR4435-2HG to regulate glutamine metabolism remodeling and promote the development of FH-deficient renal cell carcinoma.Cell death & disease · 2024Article
- The Tricarboxylic Acid Cycle Metabolites for Cancer: Friend or Enemy.Research (Washington, D.C.) · 2024Review
- Genomic profiling and molecular characterization of non-clear cell renal cell carcinoma: a narrative review from a clinical perspective.Therapeutic advances in medical oncology · 2024Review
- Fumarate hydratase (FH) and cancer: a paradigm of oncometabolism.British journal of cancer · 2023Review
- FH Variant Pathogenicity Promotes Purine Salvage Pathway Dependence in Kidney Cancer.Cancer discovery · 2023Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundLoss of function of fumarate hydratase (FH), the mitochondrial tumor suppressor and tricarboxylic acid (TCA) cycle enzyme, is associated with a highly malignant form of papillary and collecting duct renal cell cancer. The accumulation of fumarate in these cells has been linked to the tumorigenic process. However, little is known about the overall effects of the loss of FH on cellular metabolism.
methodsWe performed comprehensive metabolomic analyses of urine from Fh1-deficient mice and stable isotopologue tracing from human and mouse FH-deficient cell lines to investigate the biochemical signature of the loss of FH.
resultsThe metabolomics analysis revealed that the urea cycle metabolite argininosuccinate is a common metabolic biomarker of FH deficiency. Argininosuccinate was found to be produced from arginine and fumarate by the reverse activity of the urea cycle enzyme argininosuccinate lyase (ASL), making these cells auxotrophic for arginine. Depleting arginine from the growth media by the addition of pegylated arginine deiminase (ADI-PEG 20) decreased the production of argininosuccinate in FH-deficient cells and reduced cell survival and proliferation.
conclusionsThese results unravel a previously unidentified correlation between fumarate accumulation and the urea cycle enzyme ASL in FH-deficient cells. The finding that FH-deficient cells become auxotrophic for arginine opens a new therapeutic perspective for the cure of hereditary leiomyomatosis and renal cell cancer (HLRCC).
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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.