Sirtuin 6 Is a Critical Epigenetic Regulator of Cancer

doi:10.1007/978-3-031-07634-3_10

Review

. 2022:100:337-360.

doi: 10.1007/978-3-031-07634-3_10.

Sirtuin 6 Is a Critical Epigenetic Regulator of Cancer

Sukanya Raghu^#¹, Arathi Bangalore Prabhashankar^#¹, Bhoomika Shivanaiah¹, Ekta Tripathi^{2

3}, Nagalingam Ravi Sundaresan⁴

Affiliations

¹ Department of Microbiology and Cell Biology, Division of Biological Sciences, Indian Institute of Science (IISc), Bengaluru, Karnataka, India.
² Department of Biotechnology, Faculty of Life and Allied Health Sciences, Ramaiah University of Applied Sciences, Bengaluru, India. ektatripathi.bt.ls@msruas.ac.in.
³ Department of Microbiology and Cell Biology, Division of Biological Sciences, Indian Institute of Science (IISc), Bengaluru, Karnataka, India. ektatripathi.bt.ls@msruas.ac.in.
⁴ Department of Microbiology and Cell Biology, Division of Biological Sciences, Indian Institute of Science (IISc), Bengaluru, Karnataka, India. rsundaresan@iisc.ac.in.

^# Contributed equally.

PMID: 36301499
DOI: 10.1007/978-3-031-07634-3_10

Review

Sirtuin 6 Is a Critical Epigenetic Regulator of Cancer

Sukanya Raghu et al. Subcell Biochem. 2022.

. 2022:100:337-360.

doi: 10.1007/978-3-031-07634-3_10.

Authors

Sukanya Raghu^#¹, Arathi Bangalore Prabhashankar^#¹, Bhoomika Shivanaiah¹, Ekta Tripathi^{2

3}, Nagalingam Ravi Sundaresan⁴

Affiliations

¹ Department of Microbiology and Cell Biology, Division of Biological Sciences, Indian Institute of Science (IISc), Bengaluru, Karnataka, India.
² Department of Biotechnology, Faculty of Life and Allied Health Sciences, Ramaiah University of Applied Sciences, Bengaluru, India. ektatripathi.bt.ls@msruas.ac.in.
³ Department of Microbiology and Cell Biology, Division of Biological Sciences, Indian Institute of Science (IISc), Bengaluru, Karnataka, India. ektatripathi.bt.ls@msruas.ac.in.
⁴ Department of Microbiology and Cell Biology, Division of Biological Sciences, Indian Institute of Science (IISc), Bengaluru, Karnataka, India. rsundaresan@iisc.ac.in.

^# Contributed equally.

PMID: 36301499
DOI: 10.1007/978-3-031-07634-3_10

Abstract

Sirtuin 6 (SIRT6) is a member of the mammalian sirtuin family with deacetylase, deacylase, and mono-ADP-ribosyl-transferase activities. It is a multitasking chromatin-associated protein regulating different cellular and physiological functions in cells. Specifically, SIRT6 dysfunction is implicated in several aging-related human diseases, including cancer. Studies indicate that SIRT6 has a tumor-specific role, and it is considered a tumor suppressor as well as a tumor growth inducer, depending on the type of cancer. In this chapter, we review the role of SIRT6 in metabolism, genomic stability, and cancer. Further, we provide an insight into the interplay of the tumor-suppressing and oncogenic roles of SIRT6 in cancer. Additionally, we discuss the use of small-molecule SIRT6 modulators as potential therapeutics.

Keywords: Aging; Cancer; Genome instability; Metabolism; SIRT6.

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References

1. Albani D, Polito L, Forloni G (2010) Sirtuins as novel targets for Alzheimer’s disease and other neurodegenerative disorders: experimental and genetic evidence. J Alzheimers Dis 19(1):11–26. https://doi.org/10.3233/JAD-2010-1215 - DOI - PubMed
1. Antonia C, Debora S, Stefania O, Giovanna T, Paola M, Fabio G, Veronica R, Nicoletta C, Enrico C, Marino C, Maurizio M, Micaela B, Aimable N, Michel D, Katia T, Antonino N, Mario P, Santina B, Alessio N, Francesco B, Marco G, Roberto ML, Michele C (2018) Depletion of SIRT6 enzymatic activity increases acute myeloid leukemia cells’ vulnerability to DNA-damaging agents. Haematologica 103(1):80–90. https://doi.org/10.3324/haematol.2017.176248 - DOI
1. Ardestani PM, Liang F (2012) Sub-cellular localization, expression and functions of Sirt6 during the cell cycle in HeLa cells. Nucleus 3(5):442–451. https://doi.org/10.4161/nucl.21134 - DOI - PubMed - PMC
1. Ashraf N, Zino S, Macintyre A, Kingsmore D, Payne AP, George WD, Shiels PG (2006) Altered sirtuin expression is associated with node-positive breast cancer. Br J Cancer 95(8):1056–1061. https://doi.org/10.1038/sj.bjc.6603384 - DOI - PubMed - PMC
1. Bai L, Lin G, Sun L, Liu Y, Huang X, Cao C, Guo Y, Xie C (2016) Upregulation of SIRT6 predicts poor prognosis and promotes metastasis of non-small cell lung cancer via the ERK1/2/MMP9 pathway. Oncotarget 7(26):40377–40386. https://doi.org/10.18632/oncotarget.9750 - DOI - PubMed - PMC

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[1] Albani D, Polito L, Forloni G (2010) Sirtuins as novel targets for Alzheimer’s disease and other neurodegenerative disorders: experimental and genetic evidence. J Alzheimers Dis 19(1):11–26. https://doi.org/10.3233/JAD-2010-1215 - DOI - PubMed

[2] Albani D, Polito L, Forloni G (2010) Sirtuins as novel targets for Alzheimer’s disease and other neurodegenerative disorders: experimental and genetic evidence. J Alzheimers Dis 19(1):11–26. https://doi.org/10.3233/JAD-2010-1215 - DOI - PubMed

[3] Antonia C, Debora S, Stefania O, Giovanna T, Paola M, Fabio G, Veronica R, Nicoletta C, Enrico C, Marino C, Maurizio M, Micaela B, Aimable N, Michel D, Katia T, Antonino N, Mario P, Santina B, Alessio N, Francesco B, Marco G, Roberto ML, Michele C (2018) Depletion of SIRT6 enzymatic activity increases acute myeloid leukemia cells’ vulnerability to DNA-damaging agents. Haematologica 103(1):80–90. https://doi.org/10.3324/haematol.2017.176248 - DOI

[4] Antonia C, Debora S, Stefania O, Giovanna T, Paola M, Fabio G, Veronica R, Nicoletta C, Enrico C, Marino C, Maurizio M, Micaela B, Aimable N, Michel D, Katia T, Antonino N, Mario P, Santina B, Alessio N, Francesco B, Marco G, Roberto ML, Michele C (2018) Depletion of SIRT6 enzymatic activity increases acute myeloid leukemia cells’ vulnerability to DNA-damaging agents. Haematologica 103(1):80–90. https://doi.org/10.3324/haematol.2017.176248 - DOI

[5] Ardestani PM, Liang F (2012) Sub-cellular localization, expression and functions of Sirt6 during the cell cycle in HeLa cells. Nucleus 3(5):442–451. https://doi.org/10.4161/nucl.21134 - DOI - PubMed - PMC

[6] Ardestani PM, Liang F (2012) Sub-cellular localization, expression and functions of Sirt6 during the cell cycle in HeLa cells. Nucleus 3(5):442–451. https://doi.org/10.4161/nucl.21134 - DOI - PubMed - PMC

[7] Ashraf N, Zino S, Macintyre A, Kingsmore D, Payne AP, George WD, Shiels PG (2006) Altered sirtuin expression is associated with node-positive breast cancer. Br J Cancer 95(8):1056–1061. https://doi.org/10.1038/sj.bjc.6603384 - DOI - PubMed - PMC

[8] Ashraf N, Zino S, Macintyre A, Kingsmore D, Payne AP, George WD, Shiels PG (2006) Altered sirtuin expression is associated with node-positive breast cancer. Br J Cancer 95(8):1056–1061. https://doi.org/10.1038/sj.bjc.6603384 - DOI - PubMed - PMC

[9] Bai L, Lin G, Sun L, Liu Y, Huang X, Cao C, Guo Y, Xie C (2016) Upregulation of SIRT6 predicts poor prognosis and promotes metastasis of non-small cell lung cancer via the ERK1/2/MMP9 pathway. Oncotarget 7(26):40377–40386. https://doi.org/10.18632/oncotarget.9750 - DOI - PubMed - PMC

[10] Bai L, Lin G, Sun L, Liu Y, Huang X, Cao C, Guo Y, Xie C (2016) Upregulation of SIRT6 predicts poor prognosis and promotes metastasis of non-small cell lung cancer via the ERK1/2/MMP9 pathway. Oncotarget 7(26):40377–40386. https://doi.org/10.18632/oncotarget.9750 - DOI - PubMed - PMC

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Sirtuin 6 Is a Critical Epigenetic Regulator of Cancer

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