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The functional roles of TCA cycle metabolites in cancer

Oncogene volume 40, pages 3351–3363 (2021)Cite this article

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Abstract

The tricarboxylic acid cycle (TCA cycle) has been known for decades as a hub for generating cellular energy and precursors for biosynthetic pathways. Several cancers harbor mutations that affect the integrity of this cycle, mostly at the levels of isocitrate dehydrogenase (IDH), succinate dehydrogenase (SDH), and fumarate hydratase (FH). This results in dysregulation in the production of TCA cycle metabolites and is probably implicated in cancer initiation. By modulating cellular activities, including metabolism and signaling, TCA cycle intermediates are able to impact the processes of cancer development and progression. In this review, we discuss the functional roles of the TCA cycle intermediates in suppressing or promoting the progression of cancers. A further understanding of TCA metabolites’ roles and molecular mechanisms in oncogenesis would prompt developing novel metabolite-based cancer therapy in the future.

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Fig. 1: The Influence of the TCA cycle on cancer progression.
Fig. 2: Accumulation of succinate and succinyl-CoA in SDH-deficient cells, or fumarate in FH-deficient cells promote cancer progression.

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Acknowledgements

The authors apologize to the researchers whose work was not cited because of space limitation. The authors are supported by Louisiana State University (LSU) Feist-Weiller Cancer Center (FWCC) Legacy Funds (149741373A), Intramural Research Council Support (110251225A), and the Micro Seed Funds. Figures are created with BioRender.com. We thank Patrick Simon for his contributions during the editing stage of the paper.

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  1. Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, LA, 71130, USA

    Joseph Eniafe & Shuai Jiang

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  1. Joseph Eniafe
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Correspondence to Shuai Jiang.

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Eniafe, J., Jiang, S. The functional roles of TCA cycle metabolites in cancer. Oncogene 40, 3351–3363 (2021). https://doi.org/10.1038/s41388-020-01639-8

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