Abstract
Sirtuins are a highly conserved family of nicotinamide adenine dinucleotide (NAD)-dependent protein lysine modifying enzymes. They are key regulators for a wide variety of cellular and physiological processes such as cell proliferation, differentiation, DNA damage and stress response, genome stability, cell survival, metabolism, energy homeostasis, organ development and aging. Aging is one of the major risk factors of cancer, as many of the physiological mechanisms and pathologies associated with the aging process also contribute to tumor initiation, growth and/or metastasis. This review focuses on one the mammalian sirtuins, SIRT6, which has emerged as an important regulator of longevity and appears to have multiple biochemical functions that interfere with tumor development and may be useful in cancer prevention and for site-specific treatment. The recent evidence of the role of SIRT6 in carcinogenesis is also discussed, focusing on the potential use of SIRT6 modulators in cancer nanomedicine.
Highlights
Aging is a natural process depending on time, where life progresses and cells experience maturation leading to senescence and death
This review focuses on one the mammalian sirtuins, SIRT6, which has emerged as an important regulator of longevity and appears to have multiple biochemical functions that interfere with tumor development and may be useful in cancer prevention and for site-specific treatment
The members of the Sir2 family, known as sirtuins, have emerged as principal factors in regulating cellular response to stress, compromising conditions that have been directly linked to tumorigenesis and tumor development
Summary
Aging is a natural process depending on time, where life progresses and cells experience maturation leading to senescence and death. Genomic instability seems to facilitate the origin of tumorigenic mutations that supports tumor cell survival and proliferation and can be caused by genotoxic agents (e.g., ionizing radiation or ultra-violet radiation) or metabolic reactive oxygen species (ROS) inducing DNA damage. Classified as Class III HDACs, sirtuins are a family of proteins, present in eukaryotic organisms, conserved throughout generations that are homologous to Silencing Information Regulator Sir found in yeasts These proteins perform deacetylase and/or mono-ADP (adenosine di-phosphate)-ribosyltransferase activities requiring the cellular metabolite NAD+ (nicotinamide adenine dinucleotide), interfering in many important cellular processes including regulation of metabolic pathways, cell regulation and surviving, aging and inflammation [12,13]. Evidence shows that SIRT6 is implicated in the regulation of aerobic glycolysis in tumor cells This double role in genomic stability and in metabolism can be translated into considering that SIRT6 has a tumor regulation activity [19]. This review addresses the sirtuins role in cancer pathophysiology, with a special interest of the SIRT6 action in different kinds of cancers, as well as the first efforts in SIRT6 modulators research
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