ArticleOncotarget2016
Role of isoenzyme M2 of pyruvate kinase in urothelial tumorigenesis.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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.
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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
16 citing papers in PubMed, 34 citations in OpenAlex.
- Shared Major Metabolic Pathways and Potential Targeted Therapies in Malignancies and Systemic Lupus Erythematosus.Biomolecules · 2026Review
- Targeting Glycolytic Metabolism in Cancer Therapy: Current Approaches and Future Perspectives.Cells · 2026Review
- PKM2 orchestrates tumor progression via metabolic reprogramming and MDSCs-mediated immune suppression in the tumor microenvironment.Frontiers in immunology · 2025Review
- Article
- Single-Cell FISH Analysis Reveals Distinct Shifts in PKM Isoform Populations during Drug Resistance Acquisition.Biomolecules · 2022Article
- PKM2 Is Essential for Bladder Cancer Growth and Maintenance.Cancer research · 2022Article
- Current Development and Application of Anaerobic Glycolytic Enzymes in Urothelial Cancer.International journal of molecular sciences · 2021Review
- A glycolysis-based 4-mRNA signature correlates with the prognosis and cell cycle process in patients with bladder cancer.Cancer cell international · 2020Article
- The molecular mechanisms of LncRNA-correlated PKM2 in cancer metabolism.Bioscience reports · 2019Review
- Dimethylaminomicheliolide (DMAMCL) Suppresses the Proliferation of Glioblastoma Cells via Targeting Pyruvate Kinase 2 (PKM2) and Rewiring Aerobic Glycolysis.Frontiers in oncology · 2019Article
- PKM2, function and expression and regulation.Cell & bioscience · 2019Review
- Tumor M2-PK: A novel urine marker of bladder cancer.PloS one · 2019Article
- Article
- Down-regulation of PKM2 enhances anticancer efficiency of THP on bladder cancer.Journal of cellular and molecular medicine · 2018Article
- Proceedings of the 3rd Annual Albert Institute for Bladder Cancer Research Symposium.Bladder cancer (Amsterdam, Netherlands) · 2017Article
- Inhibition of Pyruvate Kinase M2 Markedly Reduces Chemoresistance of Advanced Bladder Cancer to Cisplatin.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The conversion of precancerous lesions to full-fledged cancers requires the affected cells to surpass certain rate-limiting steps. We recently showed that activation of HRAS proto-oncogene in urothelial cells of transgenic mice causes simple urothelial hyperplasia (SUH) which is persistent and whose transition to low-grade papillary urothelial carcinoma (UC) must undergo nodular urothelial hyperplasia (NUH). We hypothesized that NUH, which has acquired fibrovascular cores, plays critical roles in mesenchymal-to-epithelial signaling, breaching the barriers of urothelial tumor initiation. Using proteomics involving two-dimensional gel electrophoresis, immunoblotting with pan-phosphotyrosine antibody and MALDI-mass spectrometry, we identified isoform 2 of pyruvate kinase (PKM2) as the major tyrosine-phosphorylated protein switched on during NUH. We extended this finding using specimens from transgenic mice, human UC and UC cell lines, establishing that PKM2, but not its spliced variant PKM1, was over-expressed in low-grade and, more prominently, high-grade UC. In muscle-invasive UC, PKM2 was co-localized with cytokeratins 5 and 14, UC progenitor markers. Specific inhibition of PKM2 by siRNA or shRNA suppressed UC cell proliferation via increased apoptosis, autophagy and unfolded protein response. These results strongly suggest that PKM2 plays an important role in the genesis of low-grade non-invasive and high-grade invasive urothelial carcinomas.
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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.