The functional roles of TCA cycle metabolites in cancer

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 dehydrogen...

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Bibliographic Details
Published in:Oncogene Vol. 40; no. 19; pp. 3351 - 3363
Main Authors: Eniafe, Joseph, Jiang, Shuai
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 13.05.2021
Nature Publishing Group
Subjects:
42/41
631/67/1059
631/67/2327
Apoptosis
Cancer
Cell Biology
Citric Acid Cycle
Dehydrogenases
Development and progression
Fumarate hydratase
Fumarate Hydratase - metabolism
Genetic aspects
Health aspects
Human Genetics
Humans
Intermediates
Internal Medicine
Isocitrate dehydrogenase
Isocitrate Dehydrogenase - metabolism
Krebs cycle
Medicine
Medicine & Public Health
Metabolites
Metabolome
Molecular modelling
Mutation
Neoplasms - genetics
Neoplasms - metabolism
Neoplasms - pathology
Oncology
Review Article
Succinate dehydrogenase
Succinate Dehydrogenase - metabolism
Tricarboxylic acid cycle
Tumorigenesis
United States
ISSN:0950-9232, 1476-5594, 1476-5594
Online Access:Get full text
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Summary: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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ISSN:0950-9232
1476-5594
1476-5594
DOI:10.1038/s41388-020-01639-8