Metabolite sensing and signaling in cancer

Metabolites are not only substrates in metabolic reactions, but also signaling molecules controlling a wide range of cellular processes. Discovery of the oncometabolite 2-hydroxyglutarate provides an important link between metabolic dysfunction and cancer, unveiling the signaling function of metabol...

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Bibliographic Details
Published in:The Journal of biological chemistry 2020-08, Vol.295 (33), p.11938-11946
Main Authors: Wang, Yi-Ping, Li, Jin-Tao, Qu, Jia, Yin, Miao, Lei, Qun-Ying
Format: Article
Language:English
Subjects:
2HG
Animals
cancer
cancer biology
cancer stem cells
Epigenesis, Genetic
Glutarates - metabolism
Humans
immunosurveillance
JBC Reviews
metabolic disease
metabolic intermediate
Metabolic Networks and Pathways
metabolic regulation
metabolite
metabolite sensing
Metabolome
Metabolomics
Neoplasms - genetics
Neoplasms - metabolism
oncogenic signaling
oncometabolite
sensing
Signal Transduction
signaling
tumor metabolism
Tumor Microenvironment
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Summary:Metabolites are not only substrates in metabolic reactions, but also signaling molecules controlling a wide range of cellular processes. Discovery of the oncometabolite 2-hydroxyglutarate provides an important link between metabolic dysfunction and cancer, unveiling the signaling function of metabolites in regulating epigenetic and epitranscriptomic modifications, genome integrity, and signal transduction. It is now known that cancer cells remodel their metabolic network to support biogenesis, caused by or resulting in the dysregulation of various metabolites. Cancer cells can sense alterations in metabolic intermediates to better coordinate multiple biological processes and enhance cell metabolism. Recent studies have demonstrated that metabolite signaling is involved in the regulation of malignant transformation, cell proliferation, epithelial-to-mesenchymal transition, differentiation blockade, and cancer stemness. Additionally, intercellular metabolite signaling modulates inflammatory response and immunosurveillance in the tumor microenvironment. Here, we review recent advances in cancer-associated metabolite signaling. An in depth understanding of metabolite signaling will provide new opportunities for the development of therapeutic interventions that target cancer.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.REV119.007624