ArticleOncotarget2015
Role and regulation of coordinately expressed de novo purine biosynthetic enzymes PPAT and PAICS in lung cancer.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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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.
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Who cites it
73 citing papers in PubMed, 112 citations in OpenAlex.
- Lung cancer metabolism: a dynamic and adaptive network.Cellular and molecular life sciences : CMLS · 2026Review
- Integrative multi-omics analysis identifies PAICS as a key regulator of epithelial-mesenchymal transition in breast cancer metastasis.Discover oncology · 2026Article
- IMP metabolic mechanisms and IMPDH targeting strategies in tumor metabolic reprogramming and therapy (Review).International journal of molecular medicine · 2026Review
- The oncogenic control of nucleotide synthesis.Oncogenesis · 2026Review
- Structural and molecular basis for allosteric regulation and catalytic coupling of human phosphoribosylformylglycinamidine synthase.Nature communications · 2026Article
- C1QBP forms a positive feedback loop with the PAICS/FAK/C-MYC axis to promote cancer cell proliferation.Oncogene · 2025Article
- Retinol-driven Gene Signatures Predict Lung Adenocarcinoma Outcomes and Highlight PAICS as a Therapeutic Opportunity.Phenomics (Cham, Switzerland) · 2025Article
- Hypoxanthine Promotes Pulmonary Vascular Remodeling and Adenosine Deaminase Is a Therapeutic Target for Pulmonary Hypertension.JACC. Basic to translational science · 2025Article
- Review
- Article
- 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
- An untargeted metabolomic analysis of acute AFB1 treatment in liver, breast, and lung cells.PloS one · 2025Article
- Mechanism research on inhibition of gastric cancerOpen medicine (Warsaw, Poland) · 2025Article
- Article
- Phosphoribosyl pyrophosphate amidotransferase: Novel biomarker and therapeutic target for nasopharyngeal carcinoma.Cancer science · 2024Article
- One-carbon-mediated purine synthesis underlies temozolomide resistance in glioblastoma.Cell death & disease · 2024Article
- Connecting dots between nucleotide biosynthesis and DNA lesion repair/bypass in cancer.Bioscience reports · 2024Review
- Integrated network pharmacology and metabolomics to reveal the mechanism of Pinellia ternata inhibiting non-small cell lung cancer cells.BMC complementary medicine and therapies · 2024Article
- Exploring Molecular Mechanisms and Biomarkers in COPD: An Overview of Current Advancements and Perspectives.International journal of molecular sciences · 2024Review
- Metabolic Profiling as an Approach to Differentiate T-Cell Acute Lymphoblastic Leukemia Cell Lines Belonging to the Same Genetic Subgroup.International journal of molecular sciences · 2024Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Cancer cells exhibit altered metabolism including aerobic glycolysis that channels several glycolytic intermediates into de novo purine biosynthetic pathway. We discovered increased expression of phosphoribosyl amidotransferase (PPAT) and phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) enzymes of de novo purine biosynthetic pathway in lung adenocarcinomas. Transcript analyses from next-generation RNA sequencing and gene expression profiling studies suggested that PPAT and PAICS can serve as prognostic biomarkers for aggressive lung adenocarcinoma. Immunohistochemical analysis of PAICS performed on tissue microarrays showed increased expression with disease progression and was significantly associated with poor prognosis. Through gene knockdown and over-expression studies we demonstrate that altering PPAT and PAICS expression modulates pyruvate kinase activity, cell proliferation and invasion. Furthermore we identified genomic amplification and aneuploidy of the divergently transcribed PPAT-PAICS genomic region in a subset of lung cancers. We also present evidence for regulation of both PPAT and PAICS and pyruvate kinase activity by L-glutamine, a co-substrate for PPAT. A glutamine antagonist, 6-Diazo-5-oxo-L-norleucine (DON) blocked glutamine mediated induction of PPAT and PAICS as well as reduced pyruvate kinase activity. In summary, this study reveals the regulatory mechanisms by which purine biosynthetic pathway enzymes PPAT and PAICS, and pyruvate kinase activity is increased and exposes an existing metabolic vulnerability in lung cancer cells that can be explored for pharmacological intervention.
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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.