Sirtuin 6 Is a Critical Epigenetic Regulator of Cancer.

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.