ArticleScientific reports2018
Sensitivity of Colorectal Cancer to Arginine Deprivation Therapy is Shaped by Differential Expression of Urea Cycle Enzymes.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 83 citations in OpenAlex.
- Targeting arginine metabolism overcomes chemotherapy resistance in aggressive-variant prostate cancers.iScience · 2026Article
- A novel recombinant arginine deiminase from Limosilactobacillus reuteri DSM 20016 demonstrates anticancer activity against colon cancer cells.Molecular biology reports · 2026Article
- Adaptive crosstalk between polyamine metabolism, translation, and autophagy sustains energy homeostasis in mammals during starvation: a scoping review.Amino acids · 2026Review
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- EasyMultiProfiler: an efficient multi-omics data integration and analysis workflow for microbiome research.Science China. Life sciences · 2026Article
- Arginine Transporters in Human Cancers: Emerging Mechanisms and Clinical Implications.Biomolecules · 2026Review
- Circulating arginine-nitric oxide pathway metabolites and nitrated fatty acids in relation to pathological features of colorectal cancer.Frontiers in molecular biosciences · 2026Article
- ZFPL1 Promotes Colorectal Cancer Progression by Stabilizing ASS1 to Drive the Urea Cycle and M2 Macrophage-Mediated Metastatic Colonization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Evodiamine Inhibits Colorectal Cancer by Downregulating ASS1 via Wnt/β-Catenin/c-MYC Pathway to Block Arginine Synthesis.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Metabolic Adaptations in Cancer Progression: Optimization Strategies and Therapeutic Targets.Cancers · 2025Review
- Urea cycle dysregulation: a new frontier in cancer metabolism and immune evasion.Cell communication and signaling : CCS · 2025Review
- Making sense of human colorectal cancer molecular subtypes: mice are stepping in.Cell death discovery · 2025Article
- Arginine Deprivation Induces Quiescence and Confers Vulnerability to Ferroptosis in Colorectal Cancer.Cancer research · 2025Article
- Molecular subtyping and functional characterization of gastric cancer using arginine metabolism-related genes.Frontiers in cell and developmental biology · 2025Article
- Multi-omics machine learning to study host-microbiome interactions in early-onset colorectal cancer.NPJ precision oncology · 2024Article
- The strain-dependent cytostatic activity of Lactococcus lactis on CRC cell lines is mediated through the release of arginine deiminase.Microbial cell factories · 2024Article
- Arginine dependency is a therapeutically exploitable vulnerability in chronic myeloid leukaemic stem cells.EMBO reports · 2023Article
- Characteristics of amino acid metabolism in colorectal cancer.World journal of clinical cases · 2023Review
- BRAFCommunications biology · 2023Article
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
Tumors deficient in the urea cycle enzymes argininosuccinate synthase-1 (ASS1) and ornithine transcarbamylase (OTC) are unable to synthesize arginine and can be targeted using arginine-deprivation therapy. Here, we show that colorectal cancers (CRCs) display negligible expression of OTC and, in subset of cases, ASS1 proteins. CRC cells fail to grow in arginine-free medium and dietary arginine deprivation slows growth of cancer cells implanted into immunocompromised mice. Moreover, we report that clinically-formulated arginine-degrading enzymes are effective anticancer drugs in CRC. Pegylated arginine deiminase (ADI-PEG20), which degrades arginine to citrulline and ammonia, affects growth of ASS1-negative cells, whereas recombinant human arginase-1 (rhArg1peg5000), which degrades arginine into urea and ornithine, is effective against a broad spectrum of OTC-negative CRC cell lines. This reflects the inability of CRC cells to recycle citrulline and ornithine into the urea cycle. Finally, we show that arginase antagonizes chemotherapeutic drugs oxaliplatin and 5-fluorouracil (5-FU), whereas ADI-PEG20 synergizes with oxaliplatin in ASS1-negative cell lines and appears to interact with 5-fluorouracil independently of ASS1 status. Overall, we conclude that CRC is amenable to arginine-deprivation therapy, but we warrant caution when combining arginine deprivation with standard chemotherapy.
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