ArticleOncogene2015
PCK2 activation mediates an adaptive response to glucose depletion in lung cancer.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers.
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Who cites it
121 citing papers in PubMed, 206 citations in OpenAlex.
- The proteomic landscape of small urinary extracellular vesicles during kidney transplantation.Journal of extracellular vesicles · 2020Trial
- Glucose and Oxygen Availability Shape Growth and Architecture of Tumor Spheroids in a Microfluidic 3D Model.Annals of biomedical engineering · 2026Article
- PCK2 Promotes Ribosome Biogenesis in Cervical Cancer Cells via Interaction with hnRNPK.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- The MAPK/ATF3/ASNS axis drives amino acid metabolic reprogramming to promote NSCLC survival under glucose deprivation.Journal of translational medicine · 2026Article
- A shift in the cellular redox state redirects aspartate for export under glucose deprivation.Cancer & metabolism · 2026Article
- Targeted metabolism creates possibilities for lung cancer treatment in the precision tumor era.Respiratory research · 2026Review
- Glucose and Lactate, Starters or Intermediates of Cancer Metabolic Rewiring.Advances in experimental medicine and biology · 2026Review
- Article
- Metabolic adaptation of glucose-deprived macrophages involves partial gluconeogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- NAC1 Regulates PCK2 Expression and Activates Truncated Gluconeogenesis for Growth Advantage in Ovarian Cancer Cells.International journal of molecular sciences · 2025Article
- 2D versus 3D tumor-on-chip models to study the impact of tumor organization on metabolic patterns in vitro.Scientific reports · 2025Article
- Dynamic single-cell metabolomics reveals cell-cell interaction between tumor cells and macrophages.Nature communications · 2025Article
- Regulation of lung cancer initiation and progression by the stem cell determinant Musashi.eLife · 2025Article
- High carbohydrate diet programs metabolic enzyme gene expression modification in F2 generation wistar rat males.Current research in physiology · 2025Article
- The cancer-induced lactate load and oncologic remodeling hypothesis: lactate as a driver of biosynthesis and epigenetics in cancer.Frontiers in oncology · 2025Article
- Development of a mitochondria-related gene signature for prognostic assessment in diffuse large B cell lymphoma.Frontiers in oncology · 2025Article
- Phosphoenolpyruvate carboxykinase-2 (PCK2) is a therapeutic target in triple-negative breast cancer.Breast cancer research and treatment · 2024Article
- Glycogenesis and glyconeogenesis from glutamine, lactate and glycerol support human macrophage functions.EMBO reports · 2024Article
- Lactylation-Driven IGF2BP3-Mediated Serine Metabolism Reprogramming and RNA m6A-Modification Promotes Lenvatinib Resistance in HCC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Transcriptomics and Metabolomics Explain the Crisping Mechanisms of Broad Bean-Based Crisping Diets on Nile Tilapia (Metabolites · 2024Article
61 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Cancer cells are reprogrammed to utilize glycolysis at high rates, which provides metabolic precursors for cell growth. Consequently, glucose levels may decrease substantially in underperfused tumor areas. Gluconeogenesis results in the generation of glucose from smaller carbon substrates such as lactate and amino acids. The key gluconeogenic enzyme, phosphoenolpyruvate carboxykinase (PEPCK), has been shown to provide metabolites for cell growth. Still, the role of gluconeogenesis in cancer is unknown. Here we show that the mitochondrial isoform of PEPCK (PCK2) is expressed and active in three lung cancer cell lines and in non-small cell lung cancer samples. PCK2 expression and activity were enhanced under low-glucose conditions. PEPCK activity was elevated threefold in lung cancer samples over normal lungs. To track the conversion of metabolites along the gluconeogenesis pathway, lung cancer cell lines were incubated with (13)C₃-lactate and label enrichment in the phosphoenolpyruvate (PEP) pool was measured. Under low glucose, all three carbons from (13)C₃-lactate appeared in the PEP pool, further supporting a conversion of lactate to pyruvate, via pyruvate carboxylase to oxaloacetate, and via PCK2 to phosphoenolpyruvate. PCK2 small interfering RNA and the pharmacological PEPCK inhibitor 3-mercaptopicolinate significantly enhanced glucose depletion-induced apoptosis in A549 and H23 cells, but not in H1299 cells. The growth of H23 multicellular spheroids was significantly reduced by 3-mercaptopicolinate. The results of this study suggest that lung cancer cells may utilize at least some steps of gluconeogenesis to overcome the detrimental metabolic situation during glucose deprivation and that in human lung cancers this pathway is activated in vivo.
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