The Two-Faced Role of SIRT6 in Cancer
Open Access
- 8 March 2021
- Vol. 13 (5), 1156
- https://doi.org/10.3390/cancers13051156
Abstract
Sirtuin 6 (SIRT6) is a NAD+-dependent nuclear deacylase and mono-ADP-ribosylase with a wide spectrum of substrates. Through its pleiotropic activities, SIRT6 modulates either directly or indirectly key processes linked to cell fate determination and oncogenesis such as DNA damage repair, metabolic homeostasis, and apoptosis. SIRT6 regulates the expression and activity of both pro-apoptotic (e.g., Bax) and anti-apoptotic factors (e.g., Bcl-2, survivin) in a context-depending manner. Mounting evidence points towards a double-faced involvement of SIRT6 in tumor onset and progression since the block or induction of apoptosis lead to opposite outcomes in cancer. Here, we discuss the features and roles of SIRT6 in the regulation of cell death and cancer, also focusing on recently discovered small molecule modulators that can be used as chemical probes to shed further light on SIRT6 cancer biology and proposed as potential new generation anticancer therapeutics.Funding Information
- PRIN 2016 (20152TE5PK, POC01_00043, RM11715C7CA6CE53, CUP B21c17000030007)
- Associazione Italiana per la Ricerca sul Cancro (19162)
- Ministero della Salute (RF-2018-12366268)
This publication has 127 references indexed in Scilit:
- Increased copy‐number and not DNA hypomethylation causes overexpression of the candidate proto‐oncogene CYP24A1 in colorectal cancerInternational Journal of Cancer, 2013
- SIRT6 protects human endothelial cells from DNA damage, telomere dysfunction, and senescenceCardiovascular Research, 2012
- SIRT6 is required for maintenance of telomere position effect in human cellsNature Communications, 2011
- miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signalingProceedings of the National Academy of Sciences of the United States of America, 2011
- Structure and Biochemical Functions of SIRT6Online Journal of Public Health Informatics, 2011
- The Histone Deacetylase Sirt6 Regulates Glucose Homeostasis via Hif1αCell, 2010
- SIRT6 Links Histone H3 Lysine 9 Deacetylation to NF-κB-Dependent Gene Expression and Organismal Life SpanCell, 2009
- SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatinNature, 2008
- The BH3-only protein Puma plays an essential role in cytokine deprivation–induced apoptosis of mast cellsBlood, 2007
- On the Origin of Cancer CellsScience, 1956