Dual Tumor Suppressor and Tumor Promoter Action of Sirtuins in Determining Malignant Phenotype

Sirtuins (SIRTs), class III histone deacetylases, are differentially expressed in several human cancers, where they display both oncogenic and tumor-suppressive properties depending on cellular context and experimental conditions. SIRTs are involved in many important biological processes and play a critical role in cancer initiation, promotion, and progression. A growing body of evidence indicates the involvement of SIRTs in regulating three important tumor processes: epithelial-to-mesenchymal transition (EMT), invasion, and metastasis. Many SIRTs are responsible for cellular metabolic reprogramming and drug resistance by inactivating cell death pathways and promoting uncontrolled proliferation. In this review, we summarize current knowledge on the role of SIRTs in cancer and discuss their puzzling dual function as tumor suppressors and tumor promoters, important for the future development of novel tailored SIRT-based cancer therapies.