TY - JOUR
T1 - Context-Dependent Roles for SIRT2 and SIRT3 in Tumor Development Upon Calorie Restriction or High Fat Diet
AU - Ahmed, Mohamed A.
AU - O'Callaghan, Carol
AU - Chang, Elliot D.
AU - Jiang, Haiyan
AU - Vassilopoulos, Athanassios
N1 - Funding Information:
We would like to thank the members of Center for Comparative Medicine (CCM)-Northwestern University, especially Tamara Cox and Matthew Castillo, for their significant help in this study. Funding. AV was supported by NCI/NIH R01CA182506, a Lefkofsky Family Foundation Innovation Research Award, and the Lynn Sage Foundation.
Publisher Copyright:
© Copyright © 2020 Ahmed, O'Callaghan, Chang, Jiang and Vassilopoulos.
PY - 2020/1/8
Y1 - 2020/1/8
N2 - Calorie restriction (CR) is considered one of the most robust ways to extend life span and reduce the risk of age-related diseases, including cancer, as shown in many different organisms, whereas opposite effects have been associated with high fat diets (HFDs). Despite the proven contribution of sirtuins in mediating the effects of CR in longevity, the involvement of these nutrient sensors, specifically, in the diet-induced effects on tumorigenesis has yet to be elucidated. Previous studies focusing on SIRT1, do not support a critical role for this sirtuin family member in CR-mediated cancer prevention. However, the contribution of other family members which exhibit strong deacetylase activity is unexplored. To fill this gap, we aimed at investigating the role of SIRT2 and SIRT3 in mediating the anti and pro-tumorigenic effect of CR and HFD, respectively. Our results provide strong evidence supporting distinct, context-dependent roles played by these two family members. SIRT2 is indispensable for the protective effect of CR against tumorigenesis. On the contrary, SIRT3 exhibited oncogenic properties in the context of HFD-induced tumorigenesis, suggesting that SIRT3 inhibition may mitigate the cancer-promoting effects of HFD. Given the different functions regulated by SIRT2 and SIRT3, unraveling downstream targets/pathways involved may provide opportunities to develop new strategies for cancer prevention.
AB - Calorie restriction (CR) is considered one of the most robust ways to extend life span and reduce the risk of age-related diseases, including cancer, as shown in many different organisms, whereas opposite effects have been associated with high fat diets (HFDs). Despite the proven contribution of sirtuins in mediating the effects of CR in longevity, the involvement of these nutrient sensors, specifically, in the diet-induced effects on tumorigenesis has yet to be elucidated. Previous studies focusing on SIRT1, do not support a critical role for this sirtuin family member in CR-mediated cancer prevention. However, the contribution of other family members which exhibit strong deacetylase activity is unexplored. To fill this gap, we aimed at investigating the role of SIRT2 and SIRT3 in mediating the anti and pro-tumorigenic effect of CR and HFD, respectively. Our results provide strong evidence supporting distinct, context-dependent roles played by these two family members. SIRT2 is indispensable for the protective effect of CR against tumorigenesis. On the contrary, SIRT3 exhibited oncogenic properties in the context of HFD-induced tumorigenesis, suggesting that SIRT3 inhibition may mitigate the cancer-promoting effects of HFD. Given the different functions regulated by SIRT2 and SIRT3, unraveling downstream targets/pathways involved may provide opportunities to develop new strategies for cancer prevention.
KW - SIRT2
KW - SIRT3
KW - aging
KW - calorie restriction
KW - cancer
KW - high fat diet
UR - http://www.scopus.com/inward/record.url?scp=85078276059&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85078276059&partnerID=8YFLogxK
U2 - 10.3389/fonc.2019.01462
DO - 10.3389/fonc.2019.01462
M3 - Article
C2 - 31970087
AN - SCOPUS:85078276059
VL - 9
JO - Frontiers in Oncology
JF - Frontiers in Oncology
SN - 2234-943X
M1 - 1462
ER -
