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, 38 (9), 750-8

Sirtuins in Cancer: A Balancing Act Between Genome Stability and Metabolism


Sirtuins in Cancer: A Balancing Act Between Genome Stability and Metabolism

Seung Min Jeong et al. Mol Cells.


Genomic instability and altered metabolism are key features of most cancers. Recent studies suggest that metabolic reprogramming is part of a systematic response to cellular DNA damage. Thus, defining the molecules that fine-tune metabolism in response to DNA damage will enhance our understanding of molecular mechanisms of tumorigenesis and have profound implications for the development of strategies for cancer therapy. Sirtuins have been established as critical regulators in cellular homeostasis and physiology. Here, we review the emerging data revealing a pivotal function of sirtuins in genome maintenance and cell metabolism, and highlight current advances about the phenotypic consequences of defects in these critical regulators in tumorigenesis. While many questions should be addressed about the regulation and context-dependent functions of sirtuins, it appears clear that sirtuins may provide a promising, exciting new avenue for cancer therapy.

Keywords: cancer; genomic stability; metabolism; sirtuins.


Fig. 1.
Fig. 1.
The regulation of metabolic response to DNA damage by SIRT4. DNA damage-induced SIRT4 represses the metabolism of glutamine (Gln) into TCA cycle, which contributes to the control of cell cycle progression and the maintenance of genomic integrity. Loss of SIRT4 leads to both increased glutaminolysis and DNA damage-induced genomic instability, resulting in tumorigenesis.
Fig. 2.
Fig. 2.
Sirtuins regulate genomic stability and metabolism. The roles of sirtuins in the DDR and cell metabolism are summarized. Oncogenic and tumor suppressive pathways are displayed in red and green, respectively.

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