At the Center of the Metabolism and Cancer Web: AMP-Activated Protein Kinase (AMPK)

Abstract

Copyright: © 2013 Buac D, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. That cancer cells display an altered metabolism was first recognized almost a century ago by Otto Warburg who noted that tumors display a shift in glucose metabolism from oxidative phosphorylation to glycolysis [1]. Since then, many reports have documented the importance of glycolysis in supplying much of the energy, proteins, and nucleotides required to fuel the largely metabolically demanding process at the core of all cancer causation: uncontrolled cell division [2-4]. Therefore, the importance of targeting cellular metabolism for cancer therapy has attracted much attention over the last decade and much of the research has primarily focused on three areas: i) metabolic and growth signaling pathways, ii) metabolic enzymes, and iii) diet and exercise. It was not until recently, however, that the major cellular energy sensor, Adenosine Monophosphate-Activated Protein Kinase (AMPK), emerged in the spotlight as a novel therapeutic target in the treatment of various cancer types. AMPK is a ubiquitously expressed tumor suppressor protein, which functions as a heterotrimeric enzyme and is activated in response to a variety of stress signals defined by a drop in the cellular ATP: AMP ratio [5,6]. Upon activation, energy consuming processes are shut down, while energy producing processes are turned up. In this way AMPK serves as a unique target for therapeutic intervention in a cancer setting as it integrates cellular growth factor signaling pathways with cellular metabolism.