ArticleCell metabolism2018
Arginase 2 Suppresses Renal Carcinoma Progression via Biosynthetic Cofactor Pyridoxal Phosphate Depletion and Increased Polyamine Toxicity.
Article in Cell metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 133 citations in OpenAlex.
- Pan-Cancer Analysis of the Immunomodulatory Roles and Prognostic Value of PDXP and Experimental Verification in SKCM.Cancer medicine · 2026Article
- T cell receptor repertoire dynamics and newly identified functional regulators of autologous tumor-infiltrating lymphocyte therapy in advanced solid tumors.Journal of translational medicine · 2026Article
- Immunometabolic Stress and Immune Suppression in Clear-Cell Renal Cell Carcinoma: Perspectives in Therapeutic Strategy.International journal of molecular sciences · 2026Review
- Loss of Arginase 2 Promotes Lung Metastasis in immune-competent hosts via Nitric Oxide Synthase 2-Dependent Th17 Response.bioRxiv : the preprint server for biology · 2026Article
- Explore the key genes and prognosis related to mitochondrial permeability transition driving necrosis gene in kidney renal clear cell carcinoma.Scientific reports · 2025Article
- Tumour sampling conditions perturb the metabolic landscape of clear cell renal cell carcinoma.Nature communications · 2025Article
- Multifaceted role of the vitamin B6 pathway in cancer: metabolism, immune interaction, and temporal and spatial regulation.Genes & development · 2025Review
- Metabolomic reprogramming of the tumor microenvironment by dual arginase inhibitor OATD-02 boosts anticancer immunity.Scientific reports · 2025Article
- Arginine: at the crossroads of nitrogen metabolism.The EMBO journal · 2025Review
- Emerging roles of metabolic biomarkers in renal cell carcinoma: from molecular mechanisms to clinical implications.Frontiers in cell and developmental biology · 2025Review
- Mitophagy-related gene TRIP13 predicts prognosis and immune response and promotes proliferation and migrationFrontiers in pharmacology · 2025Article
- Effect of liraglutide on the dysglycemia, inflammation, and gut microbiota in prediabetic KKay mice.Frontiers in pharmacology · 2025Article
- Identifying a prognostic signature for clear cell renal cell carcinoma: the convergence of single-cell and bulk sequencing with machine learning.Frontiers in cell and developmental biology · 2025Article
- Loss of Carbamoyl Phosphate Synthetase 1 Potentiates Hepatocellular Carcinoma Metastasis by Reducing Aspartate Level.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Toward a CRISPR-based mouse model ofProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Nc-RNA-mediated low expression of AZIN1 correlated with unfavorable prognosis in kidney renal clear cell carcinoma.Cancer medicine · 2024Article
- Metabolite profiling of human renal cell carcinoma reveals tissue-origin dominance in nutrient availability.eLife · 2024Article
- Bile Acid Metabolism Mediates Cholesterol Homeostasis and Promotes Tumorigenesis in Clear Cell Renal Cell Carcinoma.Cancer research · 2024Article
- Metabolite profiling of human renal cell carcinoma reveals tissue-origin dominance in nutrient availability.bioRxiv : the preprint server for biology · 2024Article
- From the Inside Out: Exposing the Roles of Urea Cycle Enzymes in Tumors and Their Micro and Macro Environments.Cold Spring Harbor perspectives in medicine · 2024Review
18 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
Abstract
Kidney cancer, one of the ten most prevalent malignancies in the world, has exhibited increased incidence over the last decade. The most common subtype is "clear cell" renal cell carcinoma (ccRCC), which features consistent metabolic abnormalities, such as highly elevated glycogen and lipid deposition. By integrating metabolomics, genomic, and transcriptomic data, we determined that enzymes in multiple metabolic pathways are universally depleted in human ccRCC tumors, which are otherwise genetically heterogeneous. Notably, the expression of key urea cycle enzymes, including arginase 2 (ARG2) and argininosuccinate synthase 1 (ASS1), is strongly repressed in ccRCC. Reduced ARG2 activity promotes ccRCC tumor growth through at least two distinct mechanisms: conserving the critical biosynthetic cofactor pyridoxal phosphate and avoiding toxic polyamine accumulation. Pharmacological approaches to restore urea cycle enzyme expression would greatly expand treatment strategies for ccRCC patients, where current therapies only benefit a subset of those afflicted with renal cancer.
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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.