Pyruvate Dehydrogenase and Tumor

Pyruvate dehydrogenase is a key enzyme which transforms pyruvate into acetyl-coenzyme A (acetyl-CoA) by pyruvate decarboxylation. Acetyl coenzyme A is the primary raw material for aerobic oxidation of glucose into the Krebs cycle. The activity of pyruvate dehydrogenase can be negatively regulated by pyruvate dehydrogenase kinase. The overall expression of pyruvate dehydrogenase kinase is increased in tumor cells, which results in the decreasing activity of pyruvate dehydrogenase with an increased glycolysis for energy even in the presence of oxygen. The increased glycolytic activity of malignant tumor cells can promote cell proliferation and inhibit apoptosis. The glycolytic microenvironment protects tumor cells from host immune system and chemotherapy resistance, and promotes tumor cells invasion and metastasis. Embryonic and adult stem cells rely on glycolysis for energy. Thus, the activity of pyruvate dehydrogenase plays an important role in regulation of cancer cell stemness.