Pyruvate kinase M2: multiple faces for conferring benefits on cancer cells.

Mayumi Tamada, Makoto Suematsu, Hideyuki Saya

Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, Tokyo, Japan.

Clinical cancer research : an official journal of the American Association for Cancer Research 2012 Oct 15

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The M2 splice isoform of pyruvate kinase (PKM2), an enzyme that catalyzes the later step of glycolysis, is a key regulator of aerobic glycolysis (known as the Warburg effect) in cancer cells. Expression and low enzymatic activity of PKM2 confer on cancer cells the glycolytic phenotype, which promotes rapid energy production and flow of glycolytic intermediates into collateral pathways to synthesize nucleic acids, amino acids, and lipids without the accumulation of reactive oxygen species. PKM2 enzymatic activity has also been shown to be negatively regulated by the interaction with CD44 adhesion molecule, which is a cell surface marker for cancer stem cells. In addition to the glycolytic functions, nonglycolytic functions of PKM2 in cancer cells are of particular interest. PKM2 is induced translocation into the nucleus, where it activates transcription of various genes by interacting with and phosphorylating specific nuclear proteins, endowing cancer cells with a survival and growth advantage. Therefore, inhibitors and activators of PKM2 are well underway to evaluate their anticancer effects and suitability for use as novel therapeutic strategies. ©2012 AACR

Citation

Mayumi Tamada, Makoto Suematsu, Hideyuki Saya. Pyruvate kinase M2: multiple faces for conferring benefits on cancer cells. Clinical cancer research : an official journal of the American Association for Cancer Research. 2012 Oct 15;18(20):5554-61