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Sirtuins in Cancer: a Balancing Act between Genome Stability and Metabolism
Seung Min Jeong1,2, Marcia C Haigis3
1Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.
Abstract:
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.
Insights
Sirtuins are crucial for maintaining genome stability and regulating cell metabolism, especially in response to DNA damage. Understanding their role offers new therapeutic strategies for cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Metabolism
Background:
- Genomic instability and altered metabolism are hallmarks of cancer.
- Metabolic reprogramming is increasingly recognized as a response to cellular DNA damage.
- Sirtuins are key regulators of cellular homeostasis and physiology.
Purpose of the Study:
- To review the role of sirtuins in genome maintenance and cell metabolism.
- To highlight the impact of sirtuin defects on tumorigenesis.
- To explore sirtuins as potential targets for cancer therapy.
Main Methods:
- Literature review of recent studies on sirtuins, DNA damage, metabolism, and cancer.
- Analysis of emerging data on sirtuin function in genome stability.
- Examination of phenotypic consequences of sirtuin dysregulation in tumorigenesis.
Main Results:
- Sirtuins play a pivotal role in genome maintenance.
- Sirtuins are critical regulators of cell metabolism, particularly in response to DNA damage.
- Defects in sirtuins are linked to tumorigenesis.
Conclusions:
- Sirtuins are integral to cellular responses to DNA damage, influencing both genome stability and metabolism.
- Dysfunctional sirtuins contribute to cancer development.
- Sirtuins represent a promising new therapeutic avenue for cancer treatment.
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