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The Warburg effect in 2012

Bayley, Jean-Pierrea; Devilee, Petera,b

doi: 10.1097/CCO.0b013e32834deb9e
CANCER BIOLOGY: Edited by Pierre Hainaut and Amelie Plymoth

Purpose of review A revival of interest in tumor metabolism is underway and here we discuss recent results with a focus on the central theme of the Warburg effect, aerobic glycolysis.

Recent findings The M2 tumor-specific isoform of pyruvate kinase has generated much interest, but it has now been reported that PKM2 is not specific to tumors. Despite this setback, the reciprocal regulation of PKM2, prolyl hydroxylase 3 and HIF-1 in a positive feedback loop shows that PKM2 is important to tumor metabolism. Hexokinase II was reported to be a crucial regulator of glycolysis in glioblastoma multiforme, and the importance of lactate dehydrogenase was underlined by evidence that a ‘lactate-based dialog’ exists between cancer cells and endothelial cells. A growing appreciation of the role of oncogenes and tumor suppressor genes in the Warburg effect was reflected in reports of the regulation of glutamine metabolism by p53, the role of c-Myc in the high glucose uptake of tumors, and the regulation of ectonucleoside triphosphate diphosphohydrolase 5 (ENTPD5) and ATP consumption by AKT. The sirtuins, SIRT3 and SIRT6, were also shown to play central roles in aerobic glycolysis and other aspects of tumor metabolism.

Summary The results discussed illustrate the growing integration of the previously distinct fields of molecular biological and metabolic cancer research and show that this synergy is beginning to yield a more complete and comprehensive understanding of the tumor cell.

aDepartment of Human Genetics

bDepartment of Pathology, Leiden University Medical Center, Leiden, The Netherlands

Correspondence to Professor Peter Devilee, PhD, Department of Human Genetics, Leiden University Medical Center, Building 2, Postzone S-04, Einthovenweg 20, 2333 ZC Leiden, The Netherlands. Tel: +31 71 5269510; fax: +31 71 5268285; e-mail: p.devilee@lumc.nl

© 2012 Lippincott Williams & Wilkins, Inc.