%0 Journal Article
%T PKM2, a Central Point of Regulation in Cancer Metabolism
%A Nicholas Wong
%A Jason De Melo
%A Damu Tang
%J International Journal of Cell Biology
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/242513
%X Aerobic glycolysis is the dominant metabolic pathway utilized by cancer cells, owing to its ability to divert glucose metabolites from ATP production towards the synthesis of cellular building blocks (nucleotides, amino acids, and lipids) to meet the demands of proliferation. The M2 isoform of pyruvate kinase (PKM2) catalyzes the final and also a rate-limiting reaction in the glycolytic pathway. In the PK family, PKM2 is subjected to a complex regulation by both oncogenes and tumour suppressors, which allows for a fine-tone regulation of PKM2 activity. The less active form of PKM2 drives glucose through the route of aerobic glycolysis, while active PKM2 directs glucose towards oxidative metabolism. Additionally, PKM2 possesses protein tyrosine kinase activity and plays a role in modulating gene expression and thereby contributing to tumorigenesis. We will discuss our current understanding of PKM2's regulation and its many contributions to tumorigenesis. 1. Introduction Metabolism lies in the heart of cell biology. Understanding how cancer cells cope with metabolic needs for their unique biology has been a focus of cancer research for many years. It began with the landmark observation reported more than 80 years ago by Otto Warburg that cancer cells consumed more glucose and produced a large amount of lactate even in a well-oxygenized environment, a process known as aerobic glycolysis or the Warburg effect [1, 2]. While normal differentiated cells maximize ATP production by mitochondrial oxidative phosphorylation of glucose under normoxic conditions, cancer cells generate much less ATP from glucose by aerobic glycolysis. Despite being less efficient in ATP production, glycolysis is a much more rapid process [3, 4]. Cancers commonly deregulate pathways that enhance glycolysis, including activation of the PI3£¿K-ATK-mTOR pathway and upregulation of HIF-1 and c-Myc [5, 6]. The increase in aerobic glycolysis together with its dynamic process in cancer cells enables glycolytic intermediates to be redirected for the biosynthesis of cellular building blocks (nucleotides, amino acids, and lipids) while also producing ATP. Therefore, the Warburg effect/aerobic glycolysis meets the demands of cancer and proliferating cells for macromolecular synthesis and energy production [7, 8]. As a result, cancer cells display enhanced glucose uptake and produce higher levels of lactate [1, 2]. The Warburg effect was explored for the common clinical detection of tumors by fluorodeoxyglucose (2-deoxy-2-(18F)fluoro-D-glucose) positron emission tomography (FDG-PET) [7]. In the
%U http://www.hindawi.com/journals/ijcb/2013/242513/