The emerging role and targetability of the TCA cycle in cancer metabolism
ABSTRACT The tricarboxylic acid (TCA) cycle is a central route for oxidative phosphorylation in cells, and fulfills their bioenergetic, biosynthetic, and redox balance requirements. Despite early dogma that cancer cells bypass the TCA cycle and primarily utilize aerobic glycolysis, emerging evidence...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Oxford University Press
2017-07-01
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| Series: | Protein & Cell |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1007/s13238-017-0451-1 |
| _version_ | 1797716196219420672 |
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| author | Nicole M. Anderson Patrick Mucka Joseph G. Kern Hui Feng |
| author_facet | Nicole M. Anderson Patrick Mucka Joseph G. Kern Hui Feng |
| author_sort | Nicole M. Anderson |
| collection | DOAJ |
| description | ABSTRACT The tricarboxylic acid (TCA) cycle is a central route for oxidative phosphorylation in cells, and fulfills their bioenergetic, biosynthetic, and redox balance requirements. Despite early dogma that cancer cells bypass the TCA cycle and primarily utilize aerobic glycolysis, emerging evidence demonstrates that certain cancer cells, especially those with deregulated oncogene and tumor suppressor expression, rely heavily on the TCA cycle for energy production and macromolecule synthesis. As the field progresses, the importance of aberrant TCA cycle function in tumorigenesis and the potentials of applying small molecule inhibitors to perturb the enhanced cycle function for cancer treatment start to evolve. In this review, we summarize current knowledge about the fuels feeding the cycle, effects of oncogenes and tumor suppressors on fuel and cycle usage, common genetic alterations and deregulation of cycle enzymes, and potential therapeutic opportunities for targeting the TCA cycle in cancer cells. With the application of advanced technology and in vivo model organism studies, it is our hope that studies of this previously overlooked biochemical hub will provide fresh insights into cancer metabolism and tumorigenesis, subsequently revealing vulnerabilities for therapeutic interventions in various cancer types. |
| first_indexed | 2024-03-12T08:17:59Z |
| format | Article |
| id | doaj.art-95ec30fd4d80421e927f1fb612740eef |
| institution | Directory Open Access Journal |
| issn | 1674-800X 1674-8018 |
| language | English |
| last_indexed | 2024-03-12T08:17:59Z |
| publishDate | 2017-07-01 |
| publisher | Oxford University Press |
| record_format | Article |
| series | Protein & Cell |
| spelling | doaj.art-95ec30fd4d80421e927f1fb612740eef2023-09-02T18:41:17ZengOxford University PressProtein & Cell1674-800X1674-80182017-07-019221623710.1007/s13238-017-0451-1The emerging role and targetability of the TCA cycle in cancer metabolismNicole M. Anderson0Patrick Mucka1Joseph G. Kern2Hui Feng3Abramson Family Cancer Research Institute, University of PennsylvaniaDepartments of Pharmacology and Medicine, The Center for Cancer Research, Section of Hematology and Medical Oncology, Boston University School of MedicineProgram in Biomedical Sciences, Boston University School of MedicineDepartments of Pharmacology and Medicine, The Center for Cancer Research, Section of Hematology and Medical Oncology, Boston University School of MedicineABSTRACT The tricarboxylic acid (TCA) cycle is a central route for oxidative phosphorylation in cells, and fulfills their bioenergetic, biosynthetic, and redox balance requirements. Despite early dogma that cancer cells bypass the TCA cycle and primarily utilize aerobic glycolysis, emerging evidence demonstrates that certain cancer cells, especially those with deregulated oncogene and tumor suppressor expression, rely heavily on the TCA cycle for energy production and macromolecule synthesis. As the field progresses, the importance of aberrant TCA cycle function in tumorigenesis and the potentials of applying small molecule inhibitors to perturb the enhanced cycle function for cancer treatment start to evolve. In this review, we summarize current knowledge about the fuels feeding the cycle, effects of oncogenes and tumor suppressors on fuel and cycle usage, common genetic alterations and deregulation of cycle enzymes, and potential therapeutic opportunities for targeting the TCA cycle in cancer cells. With the application of advanced technology and in vivo model organism studies, it is our hope that studies of this previously overlooked biochemical hub will provide fresh insights into cancer metabolism and tumorigenesis, subsequently revealing vulnerabilities for therapeutic interventions in various cancer types.http://link.springer.com/article/10.1007/s13238-017-0451-1glutaminolysisthe TCA cyclecancer metabolismglycolysis |
| spellingShingle | Nicole M. Anderson Patrick Mucka Joseph G. Kern Hui Feng The emerging role and targetability of the TCA cycle in cancer metabolism Protein & Cell glutaminolysis the TCA cycle cancer metabolism glycolysis |
| title | The emerging role and targetability of the TCA cycle in cancer metabolism |
| title_full | The emerging role and targetability of the TCA cycle in cancer metabolism |
| title_fullStr | The emerging role and targetability of the TCA cycle in cancer metabolism |
| title_full_unstemmed | The emerging role and targetability of the TCA cycle in cancer metabolism |
| title_short | The emerging role and targetability of the TCA cycle in cancer metabolism |
| title_sort | emerging role and targetability of the tca cycle in cancer metabolism |
| topic | glutaminolysis the TCA cycle cancer metabolism glycolysis |
| url | http://link.springer.com/article/10.1007/s13238-017-0451-1 |
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