ArticleScience signaling2014
Arginine starvation impairs mitochondrial respiratory function in ASS1-deficient breast cancer cells.
Article in Science signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers.
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Who cites it
129 citing papers in PubMed, 238 citations in OpenAlex.
- Efficacy, safety, and predictive biomarkers of neoadjuvant nab-paclitaxel and pembrolizumab in hormone receptor-positive breast cancer: A randomized pilot trial.Nature communications · 2025Trial
- Amino Acids as Targets for Immunotherapy against Solid Tumors.Cell biochemistry and biophysics · 2026Review
- A novel recombinant arginine deiminase from Limosilactobacillus reuteri DSM 20016 demonstrates anticancer activity against colon cancer cells.Molecular biology reports · 2026Article
- A Tumor-Responsive Enzymatic Cascade System Inducing pH-Activable Metabolic Starvation and HBiomaterials research · 2026Article
- Article
- L-arginine metabolism in breast cancer: mechanisms and therapeutic targets.Frontiers in oncology · 2026Review
- Amino acids metabolism: a potential target for cancer treatment.Molecular cancer · 2025Review
- ASS1 facilitates T-ALL progression via the arginine-mediated mTORC1/c-Myc signaling pathway.Scientific reports · 2025Article
- The role of ASS1 in mouse embryonic stem cell differentiation into mesendoderm lineages.Stem cell research & therapy · 2025Article
- Arginine depletion potentiates standard-of-care chemo-immunotherapy in preclinical models of high-risk neuroblastoma.Journal of experimental & clinical cancer research : CR · 2025Article
- Article
- The Landscape of Cancer Metabolism as a Therapeutic Target.Pathology international · 2025Review
- Amino acid metabolism in breast cancer: pathogenic drivers and therapeutic opportunities.Protein & cell · 2025Review
- Invasive lobular carcinoma: integrated multi-omics analysis reveals silencing of Argininosuccinate synthase and upregulation of nucleotide biosynthesis in tamoxifen resistance.Cell death & disease · 2025Article
- Unraveling the therapeutic landscape of approved non-peptide macrocycles.Acta pharmaceutica Sinica. B · 2025Review
- SSRP1/SLC3A2 Axis in Arginine Transport: A New Target for Overcoming Immune Evasion and Tumor Progression in Peripheral T-Cell Lymphoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Low-Dose Salinomycin Alters Mitochondrial Function and Reprograms Global Metabolism in Burkitt Lymphoma.International journal of molecular sciences · 2025Article
- Cancer cells differentially modulate mitochondrial respiration to alter redox state and enable biomass synthesis in nutrient-limited environments.bioRxiv : the preprint server for biology · 2025Article
- Arginine Deprivation Induces Quiescence and Confers Vulnerability to Ferroptosis in Colorectal Cancer.Cancer research · 2025Article
- Etoposide-induced protein 2.4 homolog promotes argininosuccinate synthase 1 and cancer cell survival upon arginine deprivation.Cellular & molecular biology letters · 2025Article
69 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Autophagy is the principal catabolic response to nutrient starvation and is necessary to clear dysfunctional or damaged organelles, but excessive autophagy can be cytotoxic or cytostatic and contributes to cell death. Depending on the abundance of enzymes involved in molecule biosynthesis, cells can be dependent on uptake of exogenous nutrients to provide these molecules. Argininosuccinate synthetase 1 (ASS1) is a key enzyme in arginine biosynthesis, and its abundance is reduced in many solid tumors, making them sensitive to external arginine depletion. We demonstrated that prolonged arginine starvation by exposure to ADI-PEG20 (pegylated arginine deiminase) induced autophagy-dependent death of ASS1-deficient breast cancer cells, because these cells are arginine auxotrophs (dependent on uptake of extracellular arginine). Indeed, these breast cancer cells died in culture when exposed to ADI-PEG20 or cultured in the absence of arginine. Arginine starvation induced mitochondrial oxidative stress, which impaired mitochondrial bioenergetics and integrity. Furthermore, arginine starvation killed breast cancer cells in vivo and in vitro only if they were autophagy-competent. Thus, a key mechanism underlying the lethality induced by prolonged arginine starvation was the cytotoxic autophagy that occurred in response to mitochondrial damage. Last, ASS1 was either low in abundance or absent in more than 60% of 149 random breast cancer biosamples, suggesting that patients with such tumors could be candidates for arginine starvation therapy.
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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.