Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 295, Issue 33, Pages 11938-11946Publisher
ELSEVIER
DOI: 10.1074/jbc.REV119.007624
Keywords
tumor metabolism; signal transduction; cancer biology; tumor microenvironment; cancer stem cells; metabolite sensing; oncogenic signaling; 2HG; immunosurveillance; metabolic intermediate; cancer; metabolic regulation; signaling; metabolic disease; metabolomics; metabolite; oncometabolite; sensing
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Funding
- MOST [2019YFA0801703]
- Natural Science Foundation of China [81790250, 81790253, 91959202, 81872240, 81790251, 81772946, 81802745]
- Innovation Program of the Shanghai Municipal Education Commission Grant [N173606]
- CAST Young Elite Scientist Sponsorship Program [2018QNRC001]
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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.
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