Nature Medicine | Spoonful of Medicine

Two on cancer

Two papers in Nature these past few days reported on some very intriguing biology of cancer cells.

Some tumor cells have the peculiar property of acting like anaerobic cells, producing lactate even in the presence of oxygen — a property known as aerobic glycolysis or the Warburg phenomenon. The molecular mechanisms behind this phenotype are not clear, but the first of these two papers provides a very solid clue to account for it. Heather Christofk and her colleagues show that a switch between isoforms of the glycolytic enzyme pyruvate kinase is crucial for aerobic glycolysis and tumorigenesis. Tumor cells express the embryonic M2 isoform of pyruvate kinase, but by knocking it down and replacing it with the M1 (adult) isoform, the authors reversed aerobic glycolysis and reduced tumor growth in mice.

The second paper takes a look at the hardcore signaling that takes place inside tumor cells. We know very well that the Ras-PI3K-AKT pathway is crucial for tumor maintenance. The new study, by Kian-Huat Lim and colleagues, shows that blocking the AKT-mediated phosphorylation of endothelial nitric oxide synthase (eNOS) also inhibits tumor maintenance. As eNOS enhances the nitrosylation and activity of Ras proteins, which are required for tumorigenesis, the authors come full circle by proposing a (mutated) Ras-PI3K-AKT-eNOS-(wild-type) Ras pathway for tumor growth.