ArticleCell death & disease2020
Systems level profiling of arginine starvation reveals MYC and ERK adaptive metabolic reprogramming.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 18 citations in OpenAlex.
- Arginine metabolism supportsmBio · 2026Article
- Arginine Metabolism SupportsbioRxiv : the preprint server for biology · 2025Article
- Arginine depletion potentiates standard-of-care chemo-immunotherapy in preclinical models of high-risk neuroblastoma.Journal of experimental & clinical cancer research : CR · 2025Article
- Low-Dose Salinomycin Alters Mitochondrial Function and Reprograms Global Metabolism in Burkitt Lymphoma.International journal of molecular sciences · 2025Article
- Etoposide-induced protein 2.4 homolog promotes argininosuccinate synthase 1 and cancer cell survival upon arginine deprivation.Cellular & molecular biology letters · 2025Article
- Adaptation mechanisms in cancer: Lipid metabolism under hypoxia and nutrient deprivation as a target for novel therapeutic strategies (Review).Molecular medicine reports · 2025Review
- Genomic landscape and preclinical models of angiosarcoma.Molecular oncology · 2025Review
- BCL-XL Protects ASS1-Deficient Cancers from Arginine Starvation-Induced Apoptosis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Therapeutic potential of arginine deprivation therapy for gliomas: a systematic review of the existing literature.Frontiers in pharmacology · 2024Review
- Arginine depletion attenuates renal cystogenesis in tuberous sclerosis complex model.Cell reports. Medicine · 2023Article
- Targeting proliferative retinopathy: Arginase 1 limits vitreoretinal neovascularization and promotes angiogenic repair.Cell death & disease · 2022Article
- Targeted Arginine Metabolism Therapy: A Dilemma in Glioma Treatment.Frontiers in oncology · 2022Review
- Arginase: Mechanisms and Clinical Application in Hematologic Malignancy.Frontiers in oncology · 2022Review
- Arginine Signaling and Cancer Metabolism.Cancers · 2021Review
- Targeting the Proline-Glutamine-Asparagine-Arginine Metabolic Axis in Amino Acid Starvation Cancer Therapy.Pharmaceuticals (Basel, Switzerland) · 2021Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Arginine auxotrophy due to the silencing of argininosuccinate synthetase 1 (ASS1) occurs in many carcinomas and in the majority of sarcomas. Arginine deiminase (ADI-PEG20) therapy exploits this metabolic vulnerability by depleting extracellular arginine, causing arginine starvation. ASS1-negative cells develop resistance to ADI-PEG20 through a metabolic adaptation that includes re-expressing ASS1. As arginine-based multiagent therapies are being developed, further characterization of the changes induced by arginine starvation is needed. In order to develop a systems-level understanding of these changes, activity-based proteomic profiling (ABPP) and phosphoproteomic profiling were performed before and after ADI-PEG20 treatment in ADI-PEG20-sensitive and resistant sarcoma cells. When integrated with metabolomic profiling, this multi-omic analysis reveals that cellular response to arginine starvation is mediated by adaptive ERK signaling and activation of the Myc-Max transcriptional network. Concomitantly, these data elucidate proteomic changes that facilitate oxaloacetate production by enhancing glutamine and pyruvate anaplerosis and altering lipid metabolism to recycle citrate for oxidative glutaminolysis. Based on the complexity of metabolic and cellular signaling interactions, these multi-omic approaches could provide valuable tools for evaluating response to metabolically targeted therapies.
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