The Two-Faced Role of SIRT6 in Cancer.
Francesco FiorentinoVincenzo CarafaGregorio FavaleLucia AltucciAntonello MaiDante RotiliPublished in: Cancers (2021)
Sirtuin 6 (SIRT6) is a NAD+-dependent nuclear deacylase and mono-ADP-ribosylase with a wide spectrum of substrates. Through its pleiotropic activities, SIRT6 modulates either directly or indirectly key processes linked to cell fate determination and oncogenesis such as DNA damage repair, metabolic homeostasis, and apoptosis. SIRT6 regulates the expression and activity of both pro-apoptotic (e.g., Bax) and anti-apoptotic factors (e.g., Bcl-2, survivin) in a context-depending manner. Mounting evidence points towards a double-faced involvement of SIRT6 in tumor onset and progression since the block or induction of apoptosis lead to opposite outcomes in cancer. Here, we discuss the features and roles of SIRT6 in the regulation of cell death and cancer, also focusing on recently discovered small molecule modulators that can be used as chemical probes to shed further light on SIRT6 cancer biology and proposed as potential new generation anticancer therapeutics.
Keyphrases
- oxidative stress
- cell death
- small molecule
- papillary thyroid
- ischemia reperfusion injury
- dna damage
- squamous cell
- cell cycle arrest
- squamous cell carcinoma
- type diabetes
- lymph node metastasis
- adipose tissue
- photodynamic therapy
- poor prognosis
- risk assessment
- skeletal muscle
- protein protein
- metabolic syndrome
- high resolution
- dna repair
- long non coding rna
- induced apoptosis