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Sirtuins in Cancer: a Balancing Act between Genome Stability and Metabolism.

Jeong SM, Haigis MC - Mol. Cells (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department 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.

No MeSH data available.


Related in: MedlinePlus

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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f2-molce-38-9-750: 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.

Mentions: There has been a tremendous amount of advances in our understanding of the role of sirtuins in cancer. Growing evidence supports that sirtuins are clearly involved in regulating genome integrity and metabolic processes (Fig. 2), and link these two hallmarks of cancer. However, the roles of sirtuins in tumorigenesis are complex and may function as both tumor suppressor and oncogene. Thus, further work will be needed to pinpoint the exact molecular mechanisms that enabling the role of each sirtuin in cancer. Also, it remains to be determined whether sirtuins plays an important role in tumor invasion and metastasis. Last, the delineation of the interaction between sirtuins during tumorigenesis will allow for a deeper understanding of how they coordinately regulate genomic fidelity and metabolism of cancer.


Sirtuins in Cancer: a Balancing Act between Genome Stability and Metabolism.

Jeong SM, Haigis MC - Mol. Cells (2015)

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.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4588717&req=5

f2-molce-38-9-750: 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.
Mentions: There has been a tremendous amount of advances in our understanding of the role of sirtuins in cancer. Growing evidence supports that sirtuins are clearly involved in regulating genome integrity and metabolic processes (Fig. 2), and link these two hallmarks of cancer. However, the roles of sirtuins in tumorigenesis are complex and may function as both tumor suppressor and oncogene. Thus, further work will be needed to pinpoint the exact molecular mechanisms that enabling the role of each sirtuin in cancer. Also, it remains to be determined whether sirtuins plays an important role in tumor invasion and metastasis. Last, the delineation of the interaction between sirtuins during tumorigenesis will allow for a deeper understanding of how they coordinately regulate genomic fidelity and metabolism of cancer.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department 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.

No MeSH data available.


Related in: MedlinePlus