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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Haberkorn, Anne Zhang, Juan Muller, Alban Chene, Patrick Cortés-cros, Marta Hemmerlin, Christelle Ferretti, Stephane Sellers, William R. Yin, Hong Gounarides, John S. Hofmann, Francesco |
| Description | Author Affiliation: Cortés-Cros M ( Disease Area Oncology, Novartis Institutes for BioMedical Research, 4056 Basel, Switzerland. marta.cortes-cros@novartis.com); |
| Abstract | 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 2 |
| Volume Number | 110 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2013-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Glycolysis Physiology Neoplasms Physiopathology Pyruvate Kinase Metabolism Carbon Isotopes Cell Line, Tumor Chromatography, Ion Exchange DNA Primers Genetics Gene Knockdown Techniques Immunoblotting Lactic Acid Magnetic Resonance Spectroscopy Phosphoenolpyruvate Reverse Transcriptase Polymerase Chain Reaction Tandem Mass Spectrometry Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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