M2 isoform of pyruvate kinase is dispensable for tumor maintenance and growth
Open accessAbstract
Many cancer cells have increased rates of aerobic glycolysis, a phenomenon termed the Warburg effect. In addition, in tumors there is a predominance of expression of the M2 isoform of pyruvate kinase (PKM2). M2 expression was previously shown to be necessary for aerobic glycolysis and to provide a growth advantage to tumors. We report that knockdown of pyruvate kinase in tumor cells leads to a decrease in the levels of pyruvate kinase activity and an increase in the pyruvate kinase substrate phosphoenolpyruvate. However, lactate production from glucose, although reduced, was not fully inhibited. Furthermore, we are unique in reporting increased serine and glycine biosynthesis from both glucose and glutamine following pyruvate kinase knockdown. Although pyruvate kinase knockdown results in modest impairment of proliferation in vitro, in vivo growth of established xenograft tumors is unaffected by PKM2 absence. Our findings indicate that PKM2 is dispensable for tumor maintenance and growth in vivo, suggesting that other metabolic pathways bypass its function.
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Pyruvate kinase expression is dispensable for the growth of some tumors.
“but because pyruvate kinase expression is dispensable for the growth of some tumors (Cortes-Cros et al., 2013; Israelsen et al., 2013), whether pyruvate kinase activation will lead to durable responses remains an area of active study”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Cortes-Cros et al., 2013
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Self-citation
- Authors
- Cortés-Cros, M., Hemmerlin, C., Ferretti, S., Zhang, J., Gounarides, J. S., Yin, H., Muller, A., Haberkorn, A., Chene, P., Sellers, W. R., & Hofmann, F.
- Affiliations
- Novartis (Switzerland) (CH)
- Disease Area Oncology and
- Analytical Sciences and
- Disease Area Oncology, Novartis Institutes for BioMedical Research, Cambridge, MA 02138
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-12-24
- Volume
- 110
- Issue
- 2
- Pages
- 489-494
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3545759
- OpenAlex
- W2047697966
- Cited by
- 159
- References
- 19
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 6 · 2023: 2 · 2022: 8 · 2021: 18 · 2020: 8 · 2019: 15 · 2018: 19 · 2017: 16 · 2016: 11 · 2015: 16 · 2014: 20 · 2013: 11
- FWCI
- 5.08
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (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, tumor growth, Warburg effect, aerobic glycolysis, phosphoenolpyruvate, serine biosynthesis, glycine synthesis, glutamine metabolism, tumor xenografts, cancer metabolism
- MeSH terms
- Carbon Isotopes, Chromatography, Ion Exchange, Glycolysis, Humans, Neoplasms, Magnetic Resonance Spectroscopy, Phosphoenolpyruvate, Pyruvate Kinase, Immunoblotting, DNA Primers, Lactic Acid, Reverse Transcriptase Polymerase Chain Reaction, Cell Line, Tumor, Tandem Mass Spectrometry, Gene Knockdown Techniques
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