Trial reportThe Journal of clinical investigation2015
Pyruvate carboxylase is critical for non-small-cell lung cancer proliferation.
Trial report in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 337 papers.
What it found
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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.
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
337 citing papers in PubMed, 522 citations in OpenAlex.
- Does Tumor FDG-PET Avidity Represent Enhanced Glycolytic Metabolism in Non-Small Cell Lung Cancer?The Annals of thoracic surgery · 2020Trial
- Lung cancer metabolism: a dynamic and adaptive network.Cellular and molecular life sciences : CMLS · 2026Review
- Metabolic circuitry of NADH buffering reveals a vulnerability in redox-adaptive cancer cells.Innovation (Cambridge (Mass.)) · 2026Article
- 1,25D3 reprograms mitochondrial quality control via sirtuin and sensitizes glioblastoma to chemotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Adaptive plasticity of aspartate metabolism in succinate dehydrogenase-deficient cancer cells.bioRxiv : the preprint server for biology · 2026Article
- Mitochondrial copper stabilizes lipoylated TCA cycle proteins to sustain metabolism and proliferation.bioRxiv : the preprint server for biology · 2026Article
- Pyruvate carboxylase promotes SREBP1a-mediated lipid synthesis in epithelial ovarian cancer.Communications biology · 2026Article
- GLUT6-facilitated noncanonical glucose metabolic rewiring enables resistance to targeted cancer therapy.Nature communications · 2026Article
- TCA cycle rewiring underpins histone acetylation sourcing and cell-fate transitions during exit from naive pluripotency.Cell stem cell · 2026Article
- Review
- Identification of High-Performing Blood Metabolite Biomarkers of Lung Cancer in a Chinese Population.Phenomics (Cham, Switzerland) · 2026Article
- Targeting Lung Cancer Metabolism: Therapeutic Opportunities and Challenges.Advances in experimental medicine and biology · 2026Review
- Synergistic Roles of FAHD-1 and PYC-1 in Mitochondrial Function, Behavior, and Longevity in C. elegans.Advanced biology · 2026Article
- Riboflavin-PLGA nanoparticles enhance the effectiveness of the pyruvate carboxylase inhibitor ZY-444 in targeting lipogenesis in colon and breast cancer.Scientific reports · 2025Article
- Context-Specific Metabolic Alterations in HPRT1 Knockout Cells Within a 3D Culture System.Cancer medicine · 2025Article
- NMR metabolomics in genetically engineered mouse models.Biophysical reviews · 2025Review
- Methods and Guidelines for Metabolism Studies: Applications to Cancer Research.International journal of molecular sciences · 2025Review
- Lung metastases.Nature reviews. Disease primers · 2025Review
- Pyruvate Carboxylase in Macrophages Aggravates Atherosclerosis by Regulating Metabolism Reprogramming to Promote Inflammatory Responses Through the Hypoxia-Inducible Factor-1 Signaling Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Oxidative and Glycolytic Metabolism: Their Reciprocal Regulation and Dysregulation in Cancer.Cells · 2025Review
277 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Anabolic biosynthesis requires precursors supplied by the Krebs cycle, which in turn requires anaplerosis to replenish precursor intermediates. The major anaplerotic sources are pyruvate and glutamine, which require the activity of pyruvate carboxylase (PC) and glutaminase 1 (GLS1), respectively. Due to their rapid proliferation, cancer cells have increased anabolic and energy demands; however, different cancer cell types exhibit differential requirements for PC- and GLS-mediated pathways for anaplerosis and cell proliferation. Here, we infused patients with early-stage non-small-cell lung cancer (NSCLC) with uniformly 13C-labeled glucose before tissue resection and determined that the cancerous tissues in these patients had enhanced PC activity. Freshly resected paired lung tissue slices cultured in 13C6-glucose or 13C5,15N2-glutamine tracers confirmed selective activation of PC over GLS in NSCLC. Compared with noncancerous tissues, PC expression was greatly enhanced in cancerous tissues, whereas GLS1 expression showed no trend. Moreover, immunohistochemical analysis of paired lung tissues showed PC overexpression in cancer cells rather than in stromal cells of tumor tissues. PC knockdown induced multinucleation, decreased cell proliferation and colony formation in human NSCLC cells, and reduced tumor growth in a mouse xenograft model. Growth inhibition was accompanied by perturbed Krebs cycle activity, inhibition of lipid and nucleotide biosynthesis, and altered glutathione homeostasis. These findings indicate that PC-mediated anaplerosis in early-stage NSCLC is required for tumor survival and proliferation.
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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.