ArticleThe American journal of pathology2017
Argininosuccinate Synthetase 1 Loss in Invasive Bladder Cancer Regulates Survival through General Control Nonderepressible 2 Kinase-Mediated Eukaryotic Initiation Factor 2α Activity and Is Targetable by Pegylated Arginine Deiminase.
Article in The American journal of pathology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed.
- Intersection of Precision Nutrition and Bladder Cancer: A Narrative State-of-the-Art Review of Potential Applications and Challenges.Journal of clinical medicine · 2026Review
- The Multi-dimensional Mechanisms and Transformation Prospects of the Intratumoral Microbiota-Arginine Metabolism Axis in Tumor Progression and Immune Regulation.International journal of medical sciences · 2026Review
- 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
- Metabolic Signaling in the Tumor Microenvironment.Cancers · 2025Review
- Unlocking the Potential of Arginine Deprivation Therapy: Recent Breakthroughs and Promising Future for Cancer Treatment.International journal of molecular sciences · 2023Review
- The amino-acid stress sensing eIF2α kinase GCN2 is a survival biomarker for malignant mesothelioma.BJC reports · 2023Article
- PSMD2 contributes to the progression of esophageal squamous cell carcinoma by repressing autophagy.Cell & bioscience · 2023Article
- Multiple Roles of the Stress Sensor GCN2 in Immune Cells.International journal of molecular sciences · 2023Review
- A protocol to induce systemic autophagy and increase energy metabolism in mice using PEGylated arginine deiminase.STAR protocols · 2022Article
- Emerging Roles for Mammalian Target of Rapamycin (mTOR) Complexes in Bladder Cancer Progression and Therapy.Cancers · 2022Review
- Targeting Nutrient Dependency in Cancer Treatment.Frontiers in oncology · 2022Review
- The impact of physiological metabolite levels on serine uptake, synthesis and utilization in cancer cells.Nature communications · 2021Article
- Arginine Signaling and Cancer Metabolism.Cancers · 2021Review
- Transporters at the Interface between Cytosolic and Mitochondrial Amino Acid Metabolism.Metabolites · 2021Review
- Review
- Rewiring urea cycle metabolism in cancer to support anabolism.Nature reviews. Cancer · 2018Review
- Argininosuccinate Synthetase-1 (ASS1) Loss in High-Grade Neuroendocrine Carcinomas of the Urinary Bladder: Implications for Targeted Therapy with ADI-PEG 20.Endocrine pathology · 2018Article
- Rewiring of cisplatin-resistant bladder cancer cells through epigenetic regulation of genes involved in amino acid metabolism.Theranostics · 2018Article
- Drug-induced amino acid deprivation as strategy for cancer therapy.Journal of hematology & oncology · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
Abstract
Loss of argininosuccinate synthetase 1 (ASS1), a key enzyme for arginine synthesis, occurs in many cancers, making cells dependent on extracellular arginine and targetable by the arginine-degrading enzyme pegylated arginine deiminase (ADI-PEG 20). We evaluated ASS1 expression and effects of ASS1 loss in bladder cancer which, despite affecting >70,000 people in the United States annually, has limited therapies. ASS1 loss was identified in conventional and micropapillary urothelial carcinoma, small cell, and squamous cell carcinoma subtypes of invasive bladder cancer, as well as in T24, J82, and UM-UC-3 but not in 5637, RT112, and RT4 cell lines. ASS1-deficient cells showed preferential sensitivity to ADI-PEG 20, evidenced by decreased colony formation, reduced cell viability, and increased sub-G1 fractions. ADI-PEG 20 induced general control nonderepressible 2-dependent eukaryotic initiation factor 2α phosphorylation and activating transcription factor 4 and C/EBP homologous protein up-regulation, associated with caspase-independent apoptosis and autophagy. These effects were ablated with selective siRNA silencing of these proteins. ASS1 overexpression in UM-UC-3 or ASS1 silencing in RT112 cells reversed these effects. ADI-PEG 20 treatment of mice bearing contralateral flank UM-UC-3 and RT112 xenografts selectively arrested tumor growth in UM-UC-3 xenografts, which had reduced tumor size, reduced Ki-67, and increased terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining. This suggests that ASS1 loss occurs in invasive bladder cancer and is targetable by ADI-PEG 20.
Identifiers
What OpenQuestion holds
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.