Pyruvate kinase type M2 and its role in tumor growth and spreading
Abstract
Proliferating cells and tumor cells in particular express the pyruvate kinase isoenzyme type M2 (M2-PK). Within the tumor metabolome M2-PK regulates the proportions of glucose carbons that are channelled to synthetic processes (inactive dimeric form) or used for glycolytic energy production (highly active tetrameric form, a component of the glycolytic enzyme complex). In tumor cells, the dimeric form of M2-PK (Tumor M2-PK) is always predominant. The dimerization is caused by direct interaction of M2-PK with certain oncoproteins. The switch between the tetrameric and dimeric form of M2-PK allows tumor cells to survive in environments with varying oxygen und nutrient supply.
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PKM2, when highly expressed, exists in an equilibrium of enzymatically inactive pyruvate kinase dimers (or monomers) which can translocate into the nucleus, and enzymatically active tetramers which are retained in the cytosol.
“Current data indicates that PKM2, when highly expressed, exists in an equilibrium of enzymatically inactive pyruvate kinase dimers (or monomers) which can translocate into the nucleus(Christofk et al., 2008; Hitosugi et al., 2009), and enzymatically active tetramers which are retained in the cytosol(Mazurek et al., 2005).”
From Pyruvate kinase M2 regulates Hif-1α activity and IL-1β induction and is a critical determinant of the Warburg effect in LPS-activated macrophages (2015) · cites this paper as Mazurek et al., 2005
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- Authors
- Mazurek, S., Boschek, C. B., Hugo, F., & Eigenbrodt, E.
- Affiliations
- Justus-Liebig-Universität Gießen (DE)
- Corresponding author
- Mazurek, Sybille
- ORCID
- Mazurek, Sybille
- Venue
- Seminars in Cancer Biology
- Publisher
- Elsevier BV
- Published
- 2005-08
- Volume
- 15
- Issue
- 4
- Pages
- 300-308
- ISSN
- 1044-579X (ISSN-L)
- OpenAlex
- W2058650387
- Cited by
- 812
- References
- 81
- Citations by year
- 2026: 6 · 2025: 20 · 2024: 43 · 2023: 41 · 2022: 33 · 2021: 26 · 2020: 35 · 2019: 46 · 2018: 45 · 2017: 36 · 2016: 54 · 2015: 47 · 2014: 58 · 2013: 58 · 2012: 67
- FWCI
- 1.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Seminars in Cancer 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, glycolysis, enzyme dimerization, tumor growth, metastasis, tumor hypoxia, tumor cell proliferation
- MeSH terms
- Animals, Cell Division, Humans, Neoplasms, Pyruvate Kinase
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