SIRT1, is It a Tumor Promoter or Tumor Suppressor?

Overview

Journal Int J Biol Sci

Specialty Biology

Date 2009 Jan 29

PMID 19173036

Citations 182

Authors

Chu-Xia Deng

Affiliations

Soon will be listed here.

Abstract

SIRT1 has been considered as a tumor promoter because of its increased expression in some types of cancers and its role in inactivating proteins that are involved in tumor suppression and DNA damage repair. However, recent studies demonstrated that SIRT1 levels are reduced in some other types of cancers, and that SIRT1 deficiency results in genetic instability and tumorigenesis, while overexpression of SIRT1 attenuates cancer formation in mice heterozygous for tumor suppressor p53 or APC. Here, I review these recent findings and discuss the possibility that activation of SIRT1 both extends lifespan and inhibits cancer formation.

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References

Howitz K, Bitterman K, Cohen H, Lamming D, Lavu S, Wood J . Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. 2003; 425(6954):191-6. DOI: 10.1038/nature01960. View

Deng C, Brodie S . Knockout mouse models and mammary tumorigenesis. Semin Cancer Biol. 2001; 11(5):387-94. DOI: 10.1006/scbi.2001.0394. View

Blander G, Guarente L . The Sir2 family of protein deacetylases. Annu Rev Biochem. 2004; 73:417-35. DOI: 10.1146/annurev.biochem.73.011303.073651. View

Chen W, Zeng X, Carter M, Morrell C, Yen R, Esteller M . Heterozygous disruption of Hic1 predisposes mice to a gender-dependent spectrum of malignant tumors. Nat Genet. 2003; 33(2):197-202. DOI: 10.1038/ng1077. View

Haigis M, Guarente L . Mammalian sirtuins--emerging roles in physiology, aging, and calorie restriction. Genes Dev. 2006; 20(21):2913-21. DOI: 10.1101/gad.1467506. View

Lain S, Hollick J, Campbell J, Staples O, Higgins M, Aoubala M . Discovery, in vivo activity, and mechanism of action of a small-molecule p53 activator. Cancer Cell. 2008; 13(5):454-63. PMC: 2742717. DOI: 10.1016/j.ccr.2008.03.004. View

Wang R, Zheng Y, Kim H, Xu X, Cao L, Luhasen T . Interplay among BRCA1, SIRT1, and Survivin during BRCA1-associated tumorigenesis. Mol Cell. 2008; 32(1):11-20. PMC: 2577018. DOI: 10.1016/j.molcel.2008.09.011. View

Motta M, Divecha N, Lemieux M, Kamel C, Chen D, Gu W . Mammalian SIRT1 represses forkhead transcription factors. Cell. 2004; 116(4):551-63. DOI: 10.1016/s0092-8674(04)00126-6. View

Deng C . BRCA1: cell cycle checkpoint, genetic instability, DNA damage response and cancer evolution. Nucleic Acids Res. 2006; 34(5):1416-26. PMC: 1390683. DOI: 10.1093/nar/gkl010. View

10.

Dai J, Wang Z, Sun D, Lin R, Wang S . SIRT1 interacts with p73 and suppresses p73-dependent transcriptional activity. J Cell Physiol. 2006; 210(1):161-6. DOI: 10.1002/jcp.20831. View

11.

Li K, Casta A, Wang R, Lozada E, Fan W, Kane S . Regulation of WRN protein cellular localization and enzymatic activities by SIRT1-mediated deacetylation. J Biol Chem. 2008; 283(12):7590-8. DOI: 10.1074/jbc.M709707200. View

12.

Saunders L, Verdin E . Sirtuins: critical regulators at the crossroads between cancer and aging. Oncogene. 2007; 26(37):5489-504. DOI: 10.1038/sj.onc.1210616. View

13.

Milne J, Lambert P, Schenk S, Carney D, Smith J, Gagne D . Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature. 2007; 450(7170):712-6. PMC: 2753457. DOI: 10.1038/nature06261. View

14.

Guarente L . Sir2 links chromatin silencing, metabolism, and aging. Genes Dev. 2000; 14(9):1021-6. View

15.

Kim J, Chen J, Lou Z . DBC1 is a negative regulator of SIRT1. Nature. 2008; 451(7178):583-6. DOI: 10.1038/nature06500. View

16.

Wang C, Chen L, Hou X, Li Z, Kabra N, Ma Y . Interactions between E2F1 and SirT1 regulate apoptotic response to DNA damage. Nat Cell Biol. 2006; 8(9):1025-31. DOI: 10.1038/ncb1468. View

17.

Lim C . SIRT1: tumor promoter or tumor suppressor?. Med Hypotheses. 2006; 67(2):341-4. DOI: 10.1016/j.mehy.2006.01.050. View

18.

Cardiff R, Anver M, Gusterson B, Hennighausen L, Jensen R, Merino M . The mammary pathology of genetically engineered mice: the consensus report and recommendations from the Annapolis meeting. Oncogene. 2000; 19(8):968-88. DOI: 10.1038/sj.onc.1203277. View

19.

Oberdoerffer P, Michan S, McVay M, Mostoslavsky R, Vann J, Park S . SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging. Cell. 2008; 135(5):907-18. PMC: 2853975. DOI: 10.1016/j.cell.2008.10.025. View

20.

Firestein R, Blander G, Michan S, Oberdoerffer P, Ogino S, Campbell J . The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth. PLoS One. 2008; 3(4):e2020. PMC: 2289879. DOI: 10.1371/journal.pone.0002020. View