M2 isoform of pyruvate kinase is dispensable for tumor maintenance and growth.

Marta Cortés-Cros, Christelle Hemmerlin, Stephane Ferretti, Juan Zhang, John S Gounarides, Hong Yin, Alban Muller, Anne Haberkorn, Patrick Chene, William R Sellers, Francesco Hofmann

Proceedings of the National Academy of Sciences of the United States of America 2013 Jan 08

filter terms:

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.

Citation

Marta Cortés-Cros, Christelle Hemmerlin, Stephane Ferretti, Juan Zhang, John S Gounarides, Hong Yin, Alban Muller, Anne Haberkorn, Patrick Chene, William R Sellers, Francesco Hofmann. M2 isoform of pyruvate kinase is dispensable for tumor maintenance and growth. Proceedings of the National Academy of Sciences of the United States of America. 2013 Jan 08;110(2):489-94