ArticlePloS one2019
Subcellular compartmentalization of PKM2 identifies anti-PKM2 therapy response in vitro and in vivo mouse model of human non-small-cell lung cancer.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 57 citations in OpenAlex.
- Targeting Pyruvate Kinase M2: Signal Transduction Pathways and Exploration of Cancer Therapeutic Strategies.The AAPS journal · 2026Review
- A comprehensive analysis identified BECN1 as potential diagnostic biomarker for homotypic cell-in-cell in non-small cell lung cancer through integrated bioinformatics and clinical validation approaches.Discover oncology · 2026Article
- Targeting Lung Cancer Metabolism: Therapeutic Opportunities and Challenges.Advances in experimental medicine and biology · 2026Review
- PKM2 is the Metabolic Checkpoint for Stemness Features in Head and Neck Cancer.Journal of Cancer · 2026Article
- Article
- DNMT3B blocks TAL1-mediated PKM2 transcriptional repression to promote non-small cell lung cancer progression through inducing glycolysis.Cell division · 2025Article
- Metabolism, a Blossoming Target for Small-Molecule Anticancer Drugs.Molecules (Basel, Switzerland) · 2025Review
- Circular RNA hsa_circ_103089 modulates metabolic glycolysis and influences migration, invasion, and cisplatin sensitivity in non-small cell lung cancer cells via the miR-876-5p/EGFR axis.American journal of cancer research · 2025Article
- The interplay between the tumor microenvironment and tumor-derived small extracellular vesicles in cancer development and therapeutic response.Cancer biology & therapy · 2024Review
- The Illustration of Altered Glucose Dependency in Drug-Resistant Cancer Cells.International journal of molecular sciences · 2023Review
- The Ubiquitin-Proteasome System in Tumor Metabolism.Cancers · 2023Review
- Heterotypic signaling of cancer-associated fibroblasts in shaping the cancer cell drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- Pan-Cancer Analysis of the Oncogenic and Prognostic Role of PKM2: A Potential Target for Survival and Immunotherapy.BioMed research international · 2023Article
- PKM2 promotes pulmonary fibrosis by stabilizing TGF-β1 receptor I and enhancing TGF-β1 signaling.Science advances · 2022Article
- Revisited Metabolic Control and Reprogramming Cancers by Means of the Warburg Effect in Tumor Cells.International journal of molecular sciences · 2022Review
- Shikonin inhibited glycolysis and sensitized cisplatin treatment in non-small cell lung cancer cells via the exosomal pyruvate kinase M2 pathway.Bioengineered · 2022Article
- Cancer-associated fibroblasts and resistance to anticancer therapies: status, mechanisms, and countermeasures.Cancer cell international · 2022Review
- Targeting cancer metabolism in the era of precision oncology.Nature reviews. Drug discovery · 2022Review
- Targeting glycolysis in non-small cell lung cancer: Promises and challenges.Frontiers in pharmacology · 2022Review
- The role of metabolic ecosystem in cancer progression - metabolic plasticity and mTOR hyperactivity in tumor tissues.Cancer metastasis reviews · 2021Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pyruvate kinase M2 (PKM2) is an alternatively spliced variant, which mediates the conversion of glucose to lactate in cancer cells under normoxic conditions, known as the Warburg effect. Previously, we demonstrated that PKM2 is one of 97 genes that are overexpressed in non-small-cell lung cancer (NSCLC) cell lines. Herein, we demonstrate a novel role of subcellular PKM2 expression as a biomarker of therapeutic response after targeting this gene by shRNA or small molecule inhibitor (SMI) of PKM2 enzyme activity in vitro and in vivo. We examined two established lung cancer cell lines, nine patients derived NSCLC and three normal lung fibroblast cell lines for PKM2 mRNA, protein and enzyme activity by RT-qPCR, immunocytochemistry (ICC), and Western blot analysis. All eleven NSCLC cell lines showed upregulated PKM2 enzymatic activity and protein expression mainly in their cytoplasm. Targeting PKM2 by shRNA or SMI, NSCLC cells showed significantly reduced mRNA, enzyme activity, cell viability, and colony formation, which also downregulated cytosolic PKM2 and upregulated nuclear enzyme activities. Normal lung fibroblast cell lines did not express PKM2, which served as negative controls. PKM2 targeting by SMI slowed tumor growth while gene-silencing significantly reduced growth of human NSCLC xenografts. Tumor sections from responding mice showed >70% reduction in cytoplasmic PKM2 with low or undetectable nuclear staining by immunohistochemistry (IHC). In sharp contrast, non-responding tumors showed a >38% increase in PKM2 nuclear staining with low or undetectable cytoplasmic staining. In conclusion, these results confirmed PKM2 as a target for cancer therapy and an unique function of subcellular PKM2, which may characterize therapeutic response to anti-PKM2 therapy in NSCLC.
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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.