ArticleCell death & disease2024
ASS1 inhibits triple-negative breast cancer by regulating PHGDH stability and de novo serine synthesis.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- PHGDH in cancer: a narrative review of its functions beyond serine metabolism.Translational cancer research · 2026Review
- Injectable Hydrogels for Breast Cancer Therapy: From Tumor Microenvironment-Responsive and Actively Targeted Drug Delivery to Immunotherapy and Theranostics.Pharmaceutics · 2026Review
- In vitro multi-organ invasion model for exploring cardiac resistance to cancer metastasis.Nature communications · 2026Article
- Leveraging Macrophage Metabolic Reprogramming for Enhanced Anti-Tumor Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Metabolic reprogramming in cancer: dysregulation of glucose, lipid, and amino acid pathways and therapeutic opportunities.Molecular biomedicine · 2026Review
- PHGDH at the crossroads: metabolic plasticity, metastatic paradoxes, and therapeutic reconnaissance in cancer.Journal of biomedical science · 2026Review
- Mapping metabolic reprogramming in lung and breast cancer through integrative bioinformatics.PloS one · 2026Article
- L-arginine metabolism in breast cancer: mechanisms and therapeutic targets.Frontiers in oncology · 2026Review
- Amino Acid Metabolic Enzymes in Gastric Cancer: Roles and Mechanisms in Tumorigenesis and Progression.Oncology research · 2026Review
- The "serine code" of metabolic reprogramming: multidimensional roles of the serine synthesis pathway in tumors and novel breakthroughs for targeted therapy.Frontiers in immunology · 2026Review
- Novel Perspective for Prognostic Stratification and Personalized Therapy in Breast Cancer Patients: Development of Cancer Stem Cells and Metabolism-Associated Prognostic Model.International journal of women's health · 2026Article
- Serine metabolism reprogramming in cancer: a multi-tiered regulatory framework.Acta biochimica et biophysica Sinica · 2025Review
- Article
- BRCAGenie: A machine learning-driven 43-gene polygenic risk score model for precision prediction of breast cancer survival.Journal of translational medicine · 2025Article
- Interplay between malic enzyme 2, de novo serine synthesis, and the malate-aspartate shuttle drives metabolic adaptation in triple-negative breast cancer.Cancer & metabolism · 2025Article
- ASS1 inhibits liver cancer by promoting CAD ubiquitination and reversing the urea cycle and pyrimidine synthesis imbalance.Hepatology communications · 2025Article
- NSUN2 promotes colorectal cancer progression by stabilizing PHGDH mRNA to promote serine metabolism reprogramming.Cancer & metabolism · 2025Article
- Amino acid metabolism in breast cancer: pathogenic drivers and therapeutic opportunities.Protein & cell · 2025Review
- DIRAS1 Drives Oxaliplatin Resistance in Colorectal Cancer via PHB1-Mediated Mitochondrial Homeostasis.Biology · 2025Article
- Protein post-translational modifications in serine synthetic pathway: functions and molecular mechanisms.Cell communication and signaling : CCS · 2025Review
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
Argininosuccinate synthase (ASS1), a critical enzyme in the urea cycle, acts as a tumor suppressor in many cancers. To date, the anticancer mechanism of ASS1 has not been fully elucidated. Here, we found that phosphoglycerate dehydrogenase (PHGDH), a key rate-limiting enzyme in serine synthesis, is a pivotal protein that interacts with ASS1. Our results showed that ASS1 directly binds to PHGDH and promotes its ubiquitination-mediated degradation to inhibit serine synthesis, consequently suppressing tumorigenesis. Importantly, the tumor suppressive effects of ASS1 were strongly abrogated by PHGDH knockout. In addition, ASS1 knockout and knockdown partially rescued cell proliferation when serine and glycine were depleted, while the inhibitory effect of ASS1 overexpression on cell proliferation was restored by the addition of serine and glycine. These findings unveil a novel role of ASS1 and suggest that the ASS1/PHGDH serine synthesis pathway is a promising target for cancer therapy.
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