Even though this behavior can explain why SIRT6 has opposite roles in different cancer subtypes, we are cognizant that SIRT6 can also act directly and indirectly via mechanisms that are independent of its histone deacetylase activity4,5,23–25,85,91,92 and future studies will be focused on investigating additional mechanisms mediated by SIRT6-OE in our models. Here, SIRT6 is linked to cancer.