About this Research Topic
Extensive reprogramming of energy metabolism and detoxification processes are increasingly seen as critical factors involved in metastatic progression and in development of chemo- and radio-resistance. Mammal sirtuins (SIRT1-7) are a family of conserved NAD+-dependent protein deac(et)ylases and/or mono-[ADP-ribosyl]transferases with varied cellular distribution. Their role as crucial regulators in energy metabolism and adaptation to cellular stress is currently under extensive investigation worldwide, not only in physiological processes (e.g. in aging) but also in the pathogenesis of cardiovascular and neurodegenerative diseases, diabetes and cancer. In particular, sirtuin-dependent signaling is suspected to play a dual role in cell biology, on one hand protecting DNA from genomic instability and limiting the replicative potential, on the other hand inhibiting senescence and promoting survival and growth advantage. Interestingly, SIRT3-5 localize to mitochondria and regulate targets involved in a diverse array of biomolecular pathways, many of which govern energy metabolism and apoptotic death. Such characteristics confer a great importance to sirtuins, in terms of preventive medicine and therapeutic potential.
Unfortunately, despite the rapidly increasing interest in the field, results are still insufficient to draw definitive conclusions. More importantly, the question as to whether sirtuins can be considered as tumor suppressors or oncogenic proteins remains unanswered.
In this Research Topic we welcome Original Research and Review articles focused on clarifying the mechanisms underlying sirtuin-driven responses to endogenous and exogenous stressors in tumor and malignant cells, in terms of metabolic rewiring, antioxidant protection and cell cycle control. In addition, researchers are also invited to provide data and opinion regarding strategies aimed at controlling the expression and activity of sirtuin-responsive cellular systems, with particular attention to pharmacological and nutraceutical approaches. Finally, studies focused on sirtuin-dependent pathways leading to malignant progression and/or development of chemo- and radio-resistance in cancer cells are also welcome.
Potential topics include but are not strictly limited to the following:
1) In vitro or in vivo studies focused on sirtuin-dependent regulation of redox-based responses to stressors in tumor and malignant cells, with particular attention to metabolic reprogramming, DNA damage repairing capacity, antioxidative potential, and proliferation;
2) In vitro or in vivo researches on the mechanisms underlying the action of synthetic and natural compounds on the expression and activity of sirtuins and downstream cellular pathways in tumor and malignant cells;
3) In vitro or in vivo studies investigating the role of sirtuin-dependent intracellular and extracellular signaling associated with cancer progression and/or development of resistance towards chemo- and/or radio-therapies.
Keywords: sirtuin, metabolism, detoxification, malignancies, tumor
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