Abstract
Increased conversion of glucose to lactate is a key feature of many cancer cells that promotes rapid growth. Pyruvate kinase M2 (PKM2) expression is increased and facilitates lactate production in cancer cells. Modulation of PKM2 catalytic activity also regulates the synthesis of DNA and lipids that are required for cell proliferation, and of NADPH that is required for redox homeostasis. In addition to its role as a pyruvate kinase, PKM2 also functions as a protein kinase and as a transcriptional coactivator. These biochemical activities are controlled by allosteric regulators and post-translational modifications of PKM2 that include acetylation, oxidation, phosphorylation, prolyl hydroxylation, and sumoylation. Given its pleiotropic effects on cancer biology, PKM2 represents an attractive target for cancer therapy.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Carrier Proteins / antagonists & inhibitors
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Proliferation
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Cell Transformation, Neoplastic / metabolism*
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Disease Progression
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Gene Expression Regulation, Neoplastic
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Glucose / metabolism
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Humans
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Lactic Acid / metabolism
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Membrane Proteins / antagonists & inhibitors
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Neoplasm Proteins / antagonists & inhibitors
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism*
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Neoplasms / metabolism*
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Neoplasms / physiopathology
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Neoplasms / therapy
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Oxidative Stress
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Pyruvate Kinase / antagonists & inhibitors
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Pyruvate Kinase / genetics
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Pyruvate Kinase / metabolism
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Thyroid Hormone-Binding Proteins
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Thyroid Hormones / genetics
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Thyroid Hormones / metabolism*
Substances
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Carrier Proteins
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Membrane Proteins
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Neoplasm Proteins
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Thyroid Hormones
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Lactic Acid
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Pyruvate Kinase
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Glucose