ArticleOncotarget2014
Tissue-specific isoform switch and DNA hypomethylation of the pyruvate kinase PKM gene in human cancers.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers.
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Who cites it
111 citing papers in PubMed, 164 citations in OpenAlex.
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- Glycolysis and glycolytic enzymes in acute myeloid leukemia: Warburg and beyond.Frontiers in pharmacology · 2026Review
- Epigenetic reprogramming of hexokinase domain containing 1 (HKDC1) promotes proliferation in colorectal cancer.American journal of cancer research · 2026Article
- Emerging small molecule strategies target cancer stem cells through ferroptosis and metabostemness.Discover oncology · 2025Review
- Downregulation of miR-27a-3p Modulates TGF-β Signaling and Dysregulates Metabolism in Glioblastoma.International journal of molecular sciences · 2025Article
- Prognostic Value of PKM2 Expression in de novo Metastatic Colorectal Cancer Patients.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- Treatment with mitochondrial targeting antibiotics improves survival outcomes after Flock House virus infection in young and aged Drosophila melanogaster.Research square · 2025Article
- MicroRNA-122 regulates inflammatory and autophagic proteins by downregulating pyruvate kinase M2 in non-alcoholic fatty liver disease.Molecular and cellular biochemistry · 2025Article
- Review
- N6-isopentenyladenosine inhibits aerobic glycolysis in glioblastoma cells by targeting PKM2 expression and activity.FEBS open bio · 2024Article
- An in vitro neurogenetics platform for precision disease modeling in the mouse.Science advances · 2024Article
- Study on Allele Specific Expression of Long-Term Residents in High Altitude Areas.Evolutionary bioinformatics online · 2024Article
- Targeting glycolysis: exploring a new frontier in glioblastoma therapy.Frontiers in immunology · 2024Review
- Pyruvate Kinase Differentially Alters Metabolic Signatures during Head and Neck Carcinogenesis.International journal of molecular sciences · 2023Article
- Metabolic FRET sensors in intact organs: Applying spectral unmixing to acquire reliable signals.Biology open · 2023Article
- Pyruvate Kinase M (PKM) binds ribosomes in a poly-ADP ribosylation dependent manner to induce translational stalling.Nucleic acids research · 2023Article
- CAGE sequencing reveals CFTR-dependent dysregulation of type I IFN signaling in activated cystic fibrosis macrophages.Science advances · 2023Article
51 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
The M2 isoform of pyruvate kinase (PKM2) plays an important role in aerobic glycolysis and is a mediator of the Warburg effect in tumors. It was previously thought that tumor cells switch expression of PKM from normal tissue-expressed PKM1 to tumor-specific PKM2 via an alternative splicing mechanism. This view was challenged by a recent report demonstrating that PKM2 is already the major PKM isoform expressed in many differentiated normal tissues. Here, through analyses on sixteen tumor types using the cancer genome atlas RNA-Seq and exon array datasets, we confirmed that isoform switch from PKM1 to PKM2 occurred in glioblastomas but not in other tumor types examined. Despite lacking of isoform switches, PKM2 expression was found to be increased in all cancer types examined, and correlated strongly to poor prognosis in head and neck cancers. We further demonstrated that elevated PKM2 expression correlated well with the hypomethylation status of intron 1 of the PKM gene in multiple cancer types, suggesting epigenetic regulation by DNA methylation as a major mechanism in controlling PKM transcription in tumors. Our study suggests that isoform switch of PKM1 to PKM2 in cancers is tissue-specific and targeting PKM2 activity in tumors remains a promising approach for clinical intervention of multiple cancer types.
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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.