The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
The emerging role and targetability of the TCA cycle in cancer metabolism
Open accessAbstract
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.
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Citations
Cites
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Cited by
Lactate in the Regulation of Tumor Microenvironment and Therapeutic Approaches
de la Cruz-López, K. G., Castro-Muñoz, L. J., Reyes-Hernández, D. O., García-Carrancá, A., & Manzo-Merino, J. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.01143 · Cited by 940
“In the mitochondrion, glutamine is deaminated to glutamate by glutaminase (GLS), later in other deamination reaction, α-ketoglutarate is generated by the enzyme glutamate dehydrogenase (GDH) finally incorporated into TCA cycle to generate malate by fumarase enzyme since α-ketoglutarate is the major anaplerotic source…”
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Tufail, M., Jiang, C.-H., & Li, N. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02119-3 · Cited by 534
Metabolomics Reveal Nanoplastic-Induced Mitochondrial Damage in Human Liver and Lung Cells
Lin, S., Zhang, H., Wang, C., Su, X.-L., Song, Y., Wu, P., Yang, Z., Wong, M.-H., Cai, Z., & Zheng, C. (2022) · Environmental Science & Technology · doi:10.1021/acs.est.2c03980 · Cited by 391
O-GlcNAcylation of PGK1 coordinates glycolysis and TCA cycle to promote tumor growth
Nie, H., Ju, H., Fan, J., Shi, X., Cheng, Y., Cang, X., Zheng, Z., Duan, X., & Yi, W. (2020) · Nature Communications · doi:10.1038/s41467-019-13601-8 · Cited by 346
Metadata
- Authors
- Anderson, N. M., Mucka, P., Kern, J. G., & Feng, H.
- Venue
- Protein & Cell
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-07-26
- Volume
- 9
- Issue
- 2
- Pages
- 216-237
- ISSN
- 1674-800X (ISSN-L)
- 1674-8018
- OpenAlex
- W2738647095
- Cited by
- 556
- References
- 47
- FWCI
- 9.99
- Type
- journal article
- Language
- en
- Open access
- gold
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- Anderson, N. M., Mucka, P., Kern, J. G., & Feng, H. (2018). The emerging role and targetability of the TCA cycle in cancer metabolism. Protein & Cell. https://doi.org/10.1007/s13238-017-0451-1
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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