The Role for Myc in Coordinating Glycolysis, Oxidative Phosphorylation, Glutaminolysis, and Fatty Acid Metabolism in Normal and Neoplastic Tissues
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 mitocho...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-04-01
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| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fendo.2018.00129/full |
| _version_ | 1828185607922253824 |
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| author | Eric S. Goetzman Edward V. Prochownik Edward V. Prochownik Edward V. Prochownik |
| author_facet | Eric S. Goetzman Edward V. Prochownik Edward V. Prochownik Edward V. Prochownik |
| author_sort | Eric S. Goetzman |
| collection | DOAJ |
| description | 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. By 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. |
| first_indexed | 2024-04-12T07:05:54Z |
| format | Article |
| id | doaj.art-5834cc9d93aa41688d45942ce30b8c18 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-12T07:05:54Z |
| publishDate | 2018-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-5834cc9d93aa41688d45942ce30b8c182022-12-22T03:42:48ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922018-04-01910.3389/fendo.2018.00129353403The Role for Myc in Coordinating Glycolysis, Oxidative Phosphorylation, Glutaminolysis, and Fatty Acid Metabolism in Normal and Neoplastic TissuesEric S. Goetzman0Edward V. Prochownik1Edward V. Prochownik2Edward V. Prochownik3Division of Medical Genetics, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United StatesDivision of Hematology/Oncology, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United StatesDepartment of Microbiology and Molecular Genetics, University of Pittsburgh Medical Center, Pittsburgh, PA, United StatesUniversity of Pittsburgh Hillman Cancer Center, Pittsburgh, PA, United StatesThat 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. By 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.http://journal.frontiersin.org/article/10.3389/fendo.2018.00129/fullfatty acid oxidationglutaminolysisglycolysismitochondriaoxidative phosphorylationRandle cycle |
| spellingShingle | Eric S. Goetzman Edward V. Prochownik Edward V. Prochownik Edward V. Prochownik The Role for Myc in Coordinating Glycolysis, Oxidative Phosphorylation, Glutaminolysis, and Fatty Acid Metabolism in Normal and Neoplastic Tissues Frontiers in Endocrinology fatty acid oxidation glutaminolysis glycolysis mitochondria oxidative phosphorylation Randle cycle |
| title | The Role for Myc in Coordinating Glycolysis, Oxidative Phosphorylation, Glutaminolysis, and Fatty Acid Metabolism in Normal and Neoplastic Tissues |
| title_full | The Role for Myc in Coordinating Glycolysis, Oxidative Phosphorylation, Glutaminolysis, and Fatty Acid Metabolism in Normal and Neoplastic Tissues |
| title_fullStr | The Role for Myc in Coordinating Glycolysis, Oxidative Phosphorylation, Glutaminolysis, and Fatty Acid Metabolism in Normal and Neoplastic Tissues |
| title_full_unstemmed | The Role for Myc in Coordinating Glycolysis, Oxidative Phosphorylation, Glutaminolysis, and Fatty Acid Metabolism in Normal and Neoplastic Tissues |
| title_short | The Role for Myc in Coordinating Glycolysis, Oxidative Phosphorylation, Glutaminolysis, and Fatty Acid Metabolism in Normal and Neoplastic Tissues |
| title_sort | role for myc in coordinating glycolysis oxidative phosphorylation glutaminolysis and fatty acid metabolism in normal and neoplastic tissues |
| topic | fatty acid oxidation glutaminolysis glycolysis mitochondria oxidative phosphorylation Randle cycle |
| url | http://journal.frontiersin.org/article/10.3389/fendo.2018.00129/full |
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