Nonmetabolic functions of pyruvate kinase isoform M2 in controlling cell cycle progression and tumorigenesis.
Pyruvate kinase catalyzes the rate-limiting final step of glycolysis, generating adenosine triphosphate (ATP) and pyruvate. The M2 tumor-specific isoform of pyruvate kinase (PKM2) promotes glucose uptake and lactate production in the presence of oxygen, known as aerobic glycolysis or the Warburg effect. As recently reported in Nature, PKM2, besides its metabolic function, has a nonmetabolic function in the direct control of cell cycle progression by activating β-catenin and inducing expression of the β-catenin downstream gene CCND1(encoding for cyclin D1). This nonmetabolic function of PKM2 is essential for epidermal growth factor receptor (EGFR) activation-induced tumorigenesis.
Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. zhiminlu@mdanderson.org
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D000818:Animals; D002453:Cell Cycle; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D019938:Cyclin D1 / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D011770:Pyruvate Kinase / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
D007527:Isoenzymes; D051176:beta Catenin; D019938:Cyclin D1; D011770:Pyruvate Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors