ArticleCancer research2022
PKM2 Is Essential for Bladder Cancer Growth and Maintenance.
Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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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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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.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Aberrant Energy Metabolism in Tumors and Potential Therapeutic Targets.Genes, chromosomes & cancer · 2024Pooled it
- A Niacin-α-Lipoic Acid Hybrid Ameliorates Alzheimer's Disease Pathology in Mouse Models.ACS pharmacology & translational science · 2026Article
- Exosomal PKM2 from AML cells reprograms endothelial metabolism to promote angiogenesis and chemoresistance.Functional & integrative genomics · 2026Article
- OTUB1 Promotes HCC Progression by Regulating Glycolysis Through Deubiquitination of PKM2.Molecular carcinogenesis · 2026Article
- S100A10 promotes glycolysis and malignant progression of CCA by activating the HK2/ERK signaling pathway.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- SerpinB7 promotes c-Myc-mediated glycolysis by interacting with ANXA2 to facilitate the progression of non-small cell lung cancer.Molecular cancer · 2026Article
- Targeting Pyruvate Kinase M2: Signal Transduction Pathways and Exploration of Cancer Therapeutic Strategies.The AAPS journal · 2026Review
- Article
- AFP Stimulates Glucose Metabolic Reprogramming Contributing to Hepatocellular Carcinoma Resist Sorafenib Through Activating PI3K/AKT Signalling Pathway.Journal of cellular and molecular medicine · 2026Article
- Nano-bionic bacteria armed adoptive macrophage therapy against bladder cancer.Materials today. Bio · 2026Article
- Myeloid Mas drives pyruvate kinase M2-mediated Spi1 lactylation to fuel inflammatory senescence in MASLD.Signal transduction and targeted therapy · 2026Article
- PKM2 phosphorylation by c-SRC activates glycolysis and metastasis with the stimulation of tumor-associated macrophages.Cell communication and signaling : CCS · 2026Article
- The moonlighting functions of glycolytic enzymes in tumorigenesis.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Aerobic glycolysis in bladder cancer: research advances and targeted therapy potential.Frontiers in oncology · 2026Review
- The deubiquitinating enzyme UCHL3 promotes bladder cancer progression and glycolysis through enhancing PKM2 protein stability.Frontiers in oncology · 2026Article
- CEACAM6 regulates glycolytic metabolism in bladder cancer cell by controlling ENO1 stability.European journal of medical research · 2025Article
- Lactate-driven lactylation of HNRNPA1 orchestrates PKM2 splicing and glycolytic reprogramming in bladder cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- Review
- PKM2Bioactive materials · 2025Article
- PKM2 regulates angiogenic activation via ANGPT2 in endothelial cells.Scientific reports · 2025Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Pyruvate kinase M2 (PKM2) has been shown to promote tumorigenesis by facilitating the Warburg effect and enhancing the activities of oncoproteins. However, this paradigm has recently been challenged by studies in which the absence of PKM2 failed to inhibit and instead accelerated tumorigenesis in mouse models. These results seem inconsistent with the fact that most human tumors overexpress PKM2. To further elucidate the role of PKM2 in tumorigenesis, we investigated the effect of PKM2 knockout in oncogenic HRAS-driven urothelial carcinoma. While PKM2 ablation in mouse urothelial cells did not affect tumor initiation, it impaired the growth and maintenance of HRAS-driven tumors. Chemical inhibition of PKM2 recapitulated these effects. Both conditions substantially reduced complex formation of PKM2 with STAT3, their nuclear translocation, and HIF1α- and VEGF-related angiogenesis. The reduction in nuclear STAT3 in the absence of PKM2 also correlated with decreased autophagy and increased apoptosis. Time-controlled, inducible PKM2 overexpression in simple urothelial hyperplasia did not trigger tumorigenesis, while overexpression of PKM2, but not PKM1, in nodular urothelial hyperplasia with angiogenesis strongly accelerated tumorigenesis. Finally, in human patients, PKM2 was overexpressed in low-grade nonmuscle-invasive and high-grade muscle-invasive bladder cancer. Based on these data, PKM2 is not required for tumor initiation but is essential for tumor growth and maintenance by enhancing angiogenesis and metabolic addiction. The PKM2-STAT3-HIF1α/VEGF signaling axis may play a critical role in bladder cancer and may serve as an actionable therapeutic target. SIGNIFICANCE: Genetic manipulation and pharmacologic inhibition of PKM2 in mouse urothelial lesions highlight its essential role in promoting angiogenesis and metabolic addiction, events indispensable for tumor growth and maintenance.
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Registered trials
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