ArticleProceedings of the National Academy of Sciences of the United States of America2010
The alternative splicing repressors hnRNP A1/A2 and PTB influence pyruvate kinase isoform expression and cell metabolism.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 285 papers, 1 of them a synthesis that pooled it.
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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Who cites it
285 citing papers in PubMed, 1 synthesis or guideline pooled it, 426 citations in OpenAlex.
- Association between glycolysis markers and prognosis of liver cancer: a systematic review and meta-analysis.World journal of surgical oncology · 2023Pooled it
- Decreased Expression by a Chemically Modified siRNA to PTBP1 Seriously Affects Warburg Effect in Colorectal Cancer Cells.Cancer science · 2026Article
- Relationship Between PTBP1 and Pancreatic Cancer Based on microRNA and Behavior During TYMS-Mediated Carcinogenesis.Cancer science · 2026Article
- Review
- Interdependent roles of PKM2 in photoreceptors and RPE: implications for retinal degeneration.Cell death & disease · 2026Article
- Upregulated PKM2 Protects Dopaminergic Neurons From Oxidative Damage Through Nrf2 Transactivation in an MPTP-Induced Mouse Model of Parkinson's Disease.CNS neuroscience & therapeutics · 2026Article
- Spliceosome induction is a druggable dependency of RAS-driven senescence and cancer.Nature communications · 2026Article
- C3G Downregulation Enhances Stemness in Glioblastoma Cells by Promoting PKM2 Upregulation.International journal of biological sciences · 2026Article
- Cellular Distribution of Pyruvate Kinase M2 After Spinal Cord Injury in Adult Rats.Molecular neurobiology · 2025Article
- Epididymal dynamics and preimplantation roles of a sperm-enriched 5' fragment of tRNA-valine.Cell reports · 2025Article
- Deciphering splicing heterogeneity at single-cell resolution by SCSES.Nature communications · 2025Article
- Myeloid-specific HNRNPA2B1 deficiency disrupts macrophage function and in vivo responses.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Review
- miR-124/PTBP1/PKM axis modulates pulmonary artery endothelial metabolism in a pulmonary thromboembolism rat model.Journal of thoracic disease · 2025Article
- High-Resolution Molecular-Dynamics Simulations of the Pyruvate Kinase Muscle Isoform 1 and 2 (PKM1/2).Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Review
- Luminescent Lanthanides in Biorelated Applications: From Molecules to Nanoparticles and Diagnostic Probes to Therapeutics.Chemical reviews · 2025Review
- Review
- Metabolic reprogramming of glucose: the metabolic basis for the occurrence and development of hepatocellular carcinoma.Frontiers in oncology · 2025Review
- Regulation of Ptbp1-controlled alternative splicing of pyruvate kinase muscle by liver kinase B1 governs vascular smooth muscle cell plasticity in vivo.Cardiovascular research · 2024Article
225 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Cancer cells preferentially metabolize glucose by aerobic glycolysis, characterized by increased lactate production. This distinctive metabolism involves expression of the embryonic M2 isozyme of pyruvate kinase, in contrast to the M1 isozyme normally expressed in differentiated cells, and it confers a proliferative advantage to tumor cells. The M1 and M2 pyruvate-kinase isozymes are expressed from a single gene through alternative splicing of a pair of mutually exclusive exons. We measured the expression of M1 and M2 mRNA and protein isoforms in mouse tissues, tumor cell lines, and during terminal differentiation of muscle cells, and show that alternative splicing regulation is sufficient to account for the levels of expressed protein isoforms. We further show that the M1-specific exon is actively repressed in cancer-cell lines--although some M1 mRNA is expressed in cell lines derived from brain tumors--and demonstrate that the related splicing repressors hnRNP A1 and A2, as well as the polypyrimidine-tract-binding protein PTB, contribute to this control. Downregulation of these splicing repressors in cancer-cell lines using shRNAs rescues M1 isoform expression and decreases the extent of lactate production. These findings extend the links between alternative splicing and cancer, and begin to define some of the factors responsible for the switch to aerobic glycolysis.
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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.