ArticleNature cancer2020
Targeting purine synthesis in ASS1-expressing tumors enhances the response to immune checkpoint inhibitors.
Article in Nature cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 100 citations in OpenAlex.
- Mapping the functional dark proteome in cancer.Nature reviews. Cancer · 2026Review
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- PDE5A Inhibition Restricts Cancer Metastasis by Disrupting NPC1-Mediated Cholesterol Trafficking through a Noncanonical cGMP-Dependent Pathway.Cancer research · 2026Article
- GTP biosynthesis is a therapeutic vulnerability in Rac1-mutant melanoma.bioRxiv : the preprint server for biology · 2026Article
- ASS1-derived argininosuccinate promotes purine nucleoside synthesis in B cell acute lymphoblastic leukaemia.Nature metabolism · 2026Article
- Single-cell profiling uncovers extracellular vesicle-associated malignant plasma cell subpopulations driving multiple myeloma progression.Frontiers in immunology · 2026Article
- Targeting the tripartite axis of immune-metabolic-spatial crosstalk to overcome therapy resistance in breast cancer.Frontiers in immunology · 2026Review
- A 7-gene expression signature predicts immune microenvironment remodeling and neoadjuvant chemo-immunotherapy response in lung squamous cell carcinoma.Frontiers in immunology · 2026Article
- Article
- Article
- ASS1 facilitates T-ALL progression via the arginine-mediated mTORC1/c-Myc signaling pathway.Scientific reports · 2025Article
- Exploring Metabolic and Immunological Biomarkers for Oral Squamous Cell Carcinoma: Potential Targets for Precision Therapy.Biology · 2025Review
- Metabolomics and proteomics reveal blocking argininosuccinate synthetase 1 alleviates colitis in mice.Nature communications · 2025Article
- Beyond the Limit: MYC Mediates Tumor Immune Escape.Pharmaceuticals (Basel, Switzerland) · 2025Review
- PAICS-Driven Purine Biosynthesis and Its Prognostic Implications in Lung Adenocarcinoma: A Novel Risk Stratification Model and Therapeutic Insights.Current issues in molecular biology · 2025Article
- Amino acids in cancer: Understanding metabolic plasticity and divergence for better therapeutic approaches.Cell reports · 2025Review
- IMPDH inhibitors upregulate PD-L1 in cancer cells without impairing immune checkpoint inhibitor efficacy.Acta pharmacologica Sinica · 2025Article
- Proteomic Changes Associated With Endogenous FBXW7 Mutations in Moderately Differentiated Endometrial Cancer Cells Include Increased TROP2 and Galectin-3 Levels.Cancer medicine · 2025Article
- Arginine: at the crossroads of nitrogen metabolism.The EMBO journal · 2025Review
- Targeting novel regulated cell death: disulfidptosis in cancer immunotherapy with immune checkpoint inhibitors.Biomarker research · 2025Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
30 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Argininosuccinate synthase (ASS1) downregulation in different tumors has been shown to support cell proliferation and yet, in several common cancer subsets ASS1 expression associates with poor patient prognosis. Here we demonstrate that ASS1 expression under glucose deprivation is induced by c-MYC, providing survival benefit by increasing nitric oxide synthesis and activating the gluconeogenic enzymes pyruvate carboxylase and phosphoenolpyruvate carboxykinase by S-nitrosylation. The resulting increased flux through gluconeogenesis enhances serine, glycine and subsequently purine synthesis. Notably, high ASS1-expressing breast cancer mice do not respond to immune checkpoint inhibitors and patients with breast cancer with high ASS1 have more metastases. We further find that inhibiting purine synthesis increases pyrimidine to purine ratio, elevates expression of the immunoproteasome and significantly enhances the response of autologous primary CD8
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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.