1. ¹Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA
2. ²McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA

Correspondence: Dr RJ DeBerardinis, Department of Pediatrics, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Room K4.216, Dallas, TX 75390-9063, USA. E-mail: ralph.deberardinis@utsouthwestern.edu

Received 3 July 2009; Revised 14 September 2009; Accepted 23 September 2009; Published online 2 November 2009.

Abstract

Several decades of research have sought to characterize tumor cell metabolism in the hope that tumor-specific activities can be exploited to treat cancer. Having originated from Warburg's seminal observation of aerobic glycolysis in tumor cells, most of this attention has focused on glucose metabolism. However, since the 1950s cancer biologists have also recognized the importance of glutamine (Q) as a tumor nutrient. Glutamine contributes to essentially every core metabolic task of proliferating tumor cells: it participates in bioenergetics, supports cell defenses against oxidative stress and complements glucose metabolism in the production of macromolecules. The interest in glutamine metabolism has been heightened further by the recent findings that c-myc controls glutamine uptake and degradation, and that glutamine itself exerts influence over a number of signaling pathways that contribute to tumor growth. These observations are stimulating a renewed effort to understand the regulation of glutamine metabolism in tumors and to develop strategies to target glutamine metabolism in cancer. In this study we review the protean roles of glutamine in cancer, both in the direct support of tumor growth and in mediating some of the complex effects on whole-body metabolism that are characteristic of tumor progression.