Cited by 707Cancer, Hypoxia, and MetabolismMetabolism, Diabetes, and CancerCancer and biochemical research

Pyruvate kinase type M2: A key regulator of the metabolic budget system in tumor cells

Mazurek, Sybille·2011·The International Journal of Biochemistry & Cell Biology

Abstract

Cell proliferation only proceeds when metabolism is capable of providing a budget of metabolic intermediates that is adequate to ensure both energy regeneration and the synthesis of cell building blocks in sufficient amounts. In tumor cells, the glycolytic pyruvate kinase isoenzyme M2 (PKM2, M2-PK) determines whether glucose is converted to lactate for regeneration of energy (active tetrameric form, Warburg effect) or used for the synthesis of cell building blocks (nearly inactive dimeric form). This review discusses the regulation mechanisms of pyruvate kinase M2 expression by different transcription factors as well as the regulation of pyruvate kinase M2 activity by direct interaction with certain oncoproteins, tyrosine and serine phosphorylation, binding of phosphotyrosine peptides, association with other glycolytic and non glycolytic enzymes, the promyelocytic leukemia tumor suppressor protein, as well as metabolic intermediates. An intervention in the regulation mechanisms of the expression, activity and tetramer to dimer ratio of pyruvate kinase M2 has severe consequences for metabolism as well as proliferation and tumorigenic capacity of the cells which makes this enzyme a promising target for potential therapeutic approaches. The quantification of the dimeric form of pyruvate kinase M2 (Tumor M2-PK) in plasma and stool allows early detection of tumors and therapy control. Several different mechanisms may induce a translocation of pyruvate kinase M2 into the nucleus. The role of pyruvate kinase M2 in the nucleus is complex as witnessed by evidence of its effect both as pro-proliferative as well as pro-apoptotic stimuli.

Integrity signals

Registry

Crossref · 10.1016/j.biocel.2010.02.005

Cites

139 of 139 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • PKM2 splice variant is expressed in embryonic tissues, proliferating cells, and tumor cells.

    “The muscle version of PK exists as one of two isoforms, M1 or M2, generated from differential splicing of the PKM primary mRNA transcript, with the PKM2 splice variant expressed in embryonic tissues, proliferating cells, and tumor cells (54).”

Cites

Flagged first, then by citations

7 of the 146 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Authors
Mazurek, S.
Affiliations
Justus-Liebig-Universität Gießen (DE)
Corresponding author
Mazurek, Sybille
Venue
The International Journal of Biochemistry & Cell Biology
Publisher
Elsevier BV
Published
2011-07
Volume
43
Issue
7
Pages
969-980
ISSN
1357-2725 (ISSN-L)
OpenAlex
W2029255902
Cited by
694
References
146
Citations by year
2026: 14 · 2025: 41 · 2024: 39 · 2023: 46 · 2022: 35 · 2021: 52 · 2020: 35 · 2019: 42 · 2018: 52 · 2017: 46 · 2016: 41 · 2015: 63 · 2014: 50 · 2013: 60 · 2012: 49
FWCI
13.75
Type
journal article
Language
en
Open access
closed
Locations
  • The International Journal of Biochemistry & Cell Biology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
Keywords
PKM2, cancer metabolism, Warburg effect, glycolysis, transcriptional regulation, phosphotyrosine peptides, metabolic intermediates, tumor markers, nuclear translocation, apoptosis, cell proliferation, therapeutic target
MeSH terms
Animals, Cell Transformation, Neoplastic, Glucose, Glutamine, Glycolysis, Humans, Isoenzymes, Models, Biological, Neoplasm Proteins, Neoplasms, Pyruvate Kinase, Biomarkers, Tumor, Oncogene Proteins, Protein Serine-Threonine Kinases, Tumor Suppressor Proteins, Protein Interaction Mapping, Cell Proliferation, Octamer Transcription Factor-3, Mice, Rats, Metabolic Networks and Pathways

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review