The sirtuin family in cancer

Abstract

Sirtuins are a family of protein deacylases and ADP-ribosyl-transferases, homologs to the yeast SIR2 protein. Seven sirtuin paralogs have been described in mammals, with different subcellular locations, targets, enzymatic activities, and regulatory mechanisms. All sirtuins share NAD⁺ as substrate, placing them as central metabolic hubs with strong relevance in lifespan, metabolism, and cancer development. Much effort has been devoted to studying the roles of sirtuins in cancer, providing a wealth of data on sirtuins roles in mouse models and humans. Also, extensive data are available on the effects of pharmacological modulation of sirtuins in cancer development. Here, we present a comprehensive and organized resume of all the existing evidence linking every sirtuin with cancer development. From our analysis, we conclude that sirtuin modulation after tumor initiation results in unpredictable outcomes in most tumor types. On the contrary, all genetic and pharmacological models indicate that sirtuins activation prior to tumor initiation can constitute a powerful preventive strategy.