The Role for Myc in Coordinating Glycolysis, Oxphos, Glutaminolysis and Fatty Acid Metabolism in Normal and Neoplastic Tissues
- 1University of Pittsburgh, United States
That cancer cells show patterns of metabolism different from normal cells has been known for over 50 years. Yet it is only in the past decade or so that an appreciation of the benefits of these changes has begun to emerge. Altered cancer cell metabolism was initially attributed to defective mitochondria. However, we now realize that most cancers do not have mitochondrial mutations and that normal cells can transiently adopt cancer-like metabolism during periods of rapid proliferation. Indeed, an encompassing, albeit somewhat simplified, conceptual framework to explain both normal and cancer cell metabolism rests on several simple premises. First, the metabolic pathways used by cancer cells and their normal counterparts are the same. Second, normal quiescent cells use their metabolic pathways and the energy they generate largely to maintain cellular health and organelle turnover and, in some cases, to provide secreted products necessary for the survival of the intact organism. In contrast, undifferentiated cancer cells minimize the latter functions and devote their energy to producing the anabolic substrates necessary to maintain high rates of unremitting cellular proliferation. Third, as a result of the uncontrolled proliferation of cancer cells, a larger fraction of the metabolic intermediates normally used by quiescent cells purely as a source of energy are instead channeled into competing proliferation-focused and energy-consuming anabolic pathways. Fourth, cancer cell clones with the most plastic and rapidly adaptable metabolism will eventually outcompete their less well-adapted brethren during tumor progression and evolution. This attribute becomes increasingly important as tumors grow and as their individual cells compete in a constantly changing and inimical environment marked by nutrient, oxygen and growth factor deficits. Here, we review some of the metabolic pathways whose importance has gained center stage for tumor growth, particularly those under the control of the c-Myc (Myc) oncoprotein. We discuss how these pathways differ functionally between quiescent and proliferating normal cells, how they are kidnapped and corrupted during the course of transformation, and consider potential therapeutic strategies that take advantage of common features of neoplastic and metabolic disorders.
Keywords: fatty acid oxidation, Glutaminolysis, Glycolysis, Mitochondria, Oxidative Phosphorylation, Randle cycle, Warburg effect
Received: 19 Jan 2018;
Accepted: 13 Mar 2018.
Edited by:Che-Pei Kung, School of Medicine, Washington University in St. Louis, United States
Reviewed by:Eva Surmacz, Temple University, United States
Arvin Gouw, Rare Genomics Institute, United States
Copyright: © 2018 Goetzman and Prochownik. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dr. Edward V. Prochownik, University of Pittsburgh, Pittsburgh, United States, email@example.com