Fig. 1

Reprogramming of the glycolytic pathway in cancer cells. Cancer cells rely on increased glycolytic flux, increasing glucose uptake, and producing large amounts of lactate. The expression of the PKM2 isoform allows for flexibility in that the dimeric form will exhibit decreased activity, promoting accumulation of glycolytic intermediates that can be shunted into the pentose phosphate pathway and nucleotide synthesis. Decreased oxidative phosphorylation in normal cells would lead to decreased energy charge and increased AMP, activating AMPK. Cancer cells often harbor mutations in the upstream AMPK kinase LKB1, without whose phosphorylation activity, AMPK cannot be activated and therefore cannot inhibit anabolic pathways such as nucleotide synthesis