Sirtuin Biology in Cancer and Metabolic Disease: Cellular Pathways for Clinical Discovery

Title-page_2021_Sirtuin-Biology-in-Cancer-and-Metabolic-Disease
Sirtuin Biology in Cancer and Metabolic Disease
Copyright_2021_Sirtuin-Biology-in-Cancer-and-Metabolic-Disease
Copyright
Dedication_2021_Sirtuin-Biology-in-Cancer-and-Metabolic-Disease
Dedication
Contents_2021_Sirtuin-Biology-in-Cancer-and-Metabolic-Disease
Contents
List-of-contributors_2021_Sirtuin-Biology-in-Cancer-and-Metabolic-Disease
List of contributors
About-the-editor_2021_Sirtuin-Biology-in-Cancer-and-Metabolic-Disease
About the editor
Preface_2021_Sirtuin-Biology-in-Cancer-and-Metabolic-Disease
Preface
Acknowledgment_2021_Sirtuin-Biology-in-Cancer-and-Metabolic-Disease
Acknowledgment
Chapter-1---Sirtuins-in-metabolic-disease--innovat_2021_Sirtuin-Biology-in-C
1 Sirtuins in metabolic disease: innovative therapeutic strategies with SIRT1, AMPK, mTOR, and nicotinamide
Abbreviations
1.1 Noncommunicable diseases
1.2 Metabolic disorders
1.3 Novel therapeutic strategies with sirtuins for metabolic disease
1.4 Silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae)
1.5 SIRT1, metabolic function, and obesity
1.6 SIRT1 and AMP-activated protein kinase
1.7 SIRT1, mTOR, and metabolic disease
1.8 SIRT1, nicotinamide, and cellular metabolism
1.9 Future considerations
Acknowledgments
References
Chapter-2---Sirtuins-in-metabolic-and-epige_2021_Sirtuin-Biology-in-Cancer-a
2 Sirtuins in metabolic and epigenetic regulation of stem cells
2.1 Introduction
2.2 Stem cells and sirtuins
2.3 SIRT1 in stem cell biology
2.3.1 SIRT1 is important for normal embryogenesis and animal development
2.3.2 SIRT1 maintains pluripotent ESCs through multilevel mechanisms
2.3.3 SIRT1 is important for the maintenance of diverse ASC pools
2.3.4 SIRT1 is important in maintaining/promoting stemness and survival of CSCs
2.4 SIRT2 in stem cell biology
2.4.1 SIRT2 promotes differentiation of ESCs in vitro
2.4.2 SIRT2 promotes survival of CSCs
2.5 SIRT3 in stem cell biology
2.5.1 SIRT3 maintains the pool and regenerative capacity of HSCs during aging
2.6 SIRT6 in stem cell biology
2.6.1 SIRT6 epigenetically promotes proper lineage commitment of ESCs and animal development
2.6.2 SIRT6 controls regeneration and stress resistance in HSCs and mesenchymal stem cells
2.6.3 SIRT6 suppresses stemness of CSCs
2.7 SIRT7 in stem cell biology
2.7.1 SIRT7 regulates embryogenesis and life span through maintenance of genome stability
2.7.2 SIRT7 regulates quiescence and regenerative capacity of HSCs
2.8 Concluding remarks and future perspectives
References
Chapter-3---Sirtuins-and-metabolic-regulati_2021_Sirtuin-Biology-in-Cancer-a
3 Sirtuins and metabolic regulation: food and supplementation
3.1 Introduction
3.2 Tissue-specific sirtuin-modulated metabolic regulation
3.2.1 Liver
3.2.2 Adipose tissue
3.2.3 Heart and skeletal muscle
3.2.4 Kidneys
3.2.5 Pancreas
3.2.6 Brain
3.3 Nutrition as a therapeutic model for sirtuin regulation
3.3.1 Polyphenols
3.4 Resveratrol
3.5 Gallic acid
3.6 Nonresveratrol related sirtuin activators
3.7 Food and sirtuins
3.7.1 Mediterranean diet
3.7.2 Berberin
3.7.3 Green cardamom
3.7.4 Cocoa
3.7.5 Indole-3-carbinol
3.7.6 Xanthigen
3.8 Conclusion
References
Chapter-4---Sirtuins-in-diabetes-mellitus-_2021_Sirtuin-Biology-in-Cancer-an
4 Sirtuins in diabetes mellitus and diabetic kidney disease
4.1 Introduction
Part 1
4.2 Sirtuin 1 (SIRT1) in normal physiology
4.2.1 Major roles of SIRT1 in glucose metabolism
4.2.2 Major roles of SIRT1 in lipid metabolism
4.2.3 Major roles of SIRT3 in glucose metabolism and lipid metabolism
4.2.4 Major roles of SIRT4 in glucose and lipid metabolism
Part 2
4.3 Diabetes mellitus and sirtuins
4.3.1 The roles of sirtuins in the pathogenesis of diabetes mellitus
4.3.2 Sirtuins and diabetic kidney disease
4.3.2.1 What are the effects of SIRT6 and SIRT7 in kidney?
4.3.3 The roles of SIRT1 in the glomerulus in diabetic kidney disease
4.3.3.1 Results from animal models of diabetes mellitus
4.3.3.2 Results from cell culture studies
4.3.4 The roles of SIRT1 in the tubulointerstitium in diabetic kidney disease
4.3.4.1 Results from animal models of diabetes mellitus
4.3.4.2 Results from cell culture studies
4.3.5 The roles of SIRT1 and autophagy in diabetes mellitus and diabetic kidney disease
4.3.6 The roles of SIRT1 and adenosine monophosphate-activated protein kinase pathway in diabetic kidney disease
4.3.7 The roles of SIRT1 and mTOR pathway in diabetic kidney disease
4.4 Hypertension and sirtuins
4.5 Novel treatment options in diabetes mellitus and diabetic kidney disease
4.6 Conclusion and future perspectives
References
Chapter-5---Sirtuins-and-mitochondria_2021_Sirtuin-Biology-in-Cancer-and-Met
5 Sirtuins and mitochondrial dysfunction
5.1 Sirtuins are nutrient sensors
5.2 Sirtuins and mitochondrial biogenesis
5.3 Sirtuins and mitochondrial metabolism
5.4 Sirtuins and mitochondrial dysfunction in human diseases
5.4.1 Diabetes and obesity
5.4.2 Cardiovascular diseases
5.4.3 Renal disease
5.4.4 Neurodegeneration
5.4.5 Aging
5.4.6 Tumorigenesis
5.5 Feasible clinical targets: posttranslational modifications of sirtuins regulate mitochondrial function
Acknowledgments
References
Chapter-6---Sirtuins-in-immunomet_2021_Sirtuin-Biology-in-Cancer-and-Metabol
6 Sirtuins in immunometabolism
6.1 Brief introduction of immunometabolism
6.2 Role of sirtuins in immunometabolism
6.2.1 SIRT1
6.2.1.1 SIRT1 in macrophage
6.2.1.2 SIRT1 in myeloid-derived suppressor cells
6.2.1.3 SIRT1 in dendritic cells
6.2.1.4 SIRT1 in T cells
6.2.2 SIRT2
6.2.3 SIRT3, SIRT4, and SIRT5
6.2.4 SIRT6
6.2.5 SIRT7
6.3 Conclusion and future considerations
References
Chapter-7---Mitochondrial-sirtuins-at-the-crossr_2021_Sirtuin-Biology-in-Can
7 Mitochondrial sirtuins at the crossroads of energy metabolism and oncogenic transformation
Abbreviations
7.1 Introduction—advantages of possessing mitochondria
7.2 Mitochondrial sirtuins
7.3 Lipoylation of multienzymatic complexes is essential for mitochondrial metabolism
7.4 Alternative lipoylation and its metabolic consequences
7.5 Regulation of pyruvate dehydrogenase complex by mitochondrial sirtuins
7.6 Alpha ketoglutarate dehydrogenase complex regulates gene expression
7.7 Fluctuations of the intracellular concentration of organic acids has far-reaching implications
7.8 Ketogenic enzymes ACAT1 and HMGCS2 as substrates for Sirt3 and Sirt5
7.9 Antagonistic roles of mitochondrial sirtuins in fed and fasted state
7.10 The interplay between Sirt3 and isocitrate dehydrogenase in cancer cells
7.11 Tumor-suppressing and tumor-promoting activities of sirtuins in the context of glutamine and glucose metabolism
7.12 Sirtuins regulate iron–sulfur cluster assemblage
7.13 Mitochondrial fatty acid synthesis is linked to Fe–S cluster assembly and protein lipoylation—implications for cancer ...
7.14 Consequences of Fe–S cluster defects in cancer cells
7.15 Deoxyribonucleotide synthesis—toward the as yet unexplored areas of sirtuin research
7.16 Perspectives—evolutionary implications and new directions in cancer treatment
References
Chapter-8---Sirtuins-and-the-hallmar_2021_Sirtuin-Biology-in-Cancer-and-Meta
8 Sirtuins and the hallmarks of cancer
8.1 Introduction
8.2 Sirtuins in sustaining proliferative signaling and evading growth suppressors
8.3 Sirtuins and resisting cell death
8.4 Sirtuins in tumor-promoting inflammation and immune system function
8.5 Sirtuins in angiogenesis
8.6 Sirtuins in invasion and metastasis
8.7 Sirtuins in genome instability and replicative immortality
8.8 Sirtuins in reprogramming energy metabolism
8.9 Sirtuins and cancer therapy
8.10 Concluding remarks
References
Chapter-9---The-bifunctional-roles-of-sirtuins_2021_Sirtuin-Biology-in-Cance
9 The bifunctional roles of sirtuins and their therapeutic potential in cancer
9.1 The mammalian sirtuins
9.1.1 SIRT1
9.1.1.1 SIRT1 as a tumor suppressor
9.1.1.2 SIRT1 as an oncoprotein
9.1.2 SIRT2
9.1.2.1 SIRT2 as a tumor suppressor
9.1.2.2 SIRT2 as an oncoprotein
9.1.3 SIRT3
9.1.3.1 SIRT3 as a tumor suppressor
9.1.3.2 SIRT3 as an oncoprotein
9.1.4 SIRT4
9.1.4.1 SIRT4 as a tumor suppressor
9.1.4.2 SIRT4 as an oncoprotein
9.1.5 SIRT5
9.1.5.1 SIRT5 as a tumor suppressor
9.1.5.2 SIRT5 as an oncoprotein
9.1.6 SIRT6
9.1.6.1 SIRT6 as tumor suppressor
9.1.6.2 SIRT6 as an oncoprotein
9.1.7 SIRT7
9.1.7.1 SIRT7 as a tumor suppressor
9.1.7.2 SIRT7 as an oncoprotein
9.2 Sirtuin modulators
9.2.1 Sirtuin inhibitors
9.2.1.1 Nicotinamide and its analogues
9.2.1.2 β-Naphthol-containing inhibitors
9.2.1.3 Indole derivatives
9.2.1.4 Thioacyllysine-containing compounds
9.2.1.5 Tenovin
9.2.1.6 Suramin
9.2.1.7 Other SIRTi
9.2.1.7.1 AGK2
9.2.1.7.2 MHY2256
9.2.1.7.3 SirReal2
9.2.1.7.4 MC2494
9.2.1.7.5 Toxoflavin
9.2.2 Sirtuin activators
9.3 Conclusion and future perspectives
Acknowledgment
References
Chapter-10---Sirtuins-and-next-generation-hallmark_2021_Sirtuin-Biology-in-C
10 Sirtuins and next generation hallmarks of cancer: cellular energetics and tumor promoting inflammation
10.1 Introduction: an overview of sirtuins involvement in inflammation and cancer metabolism
10.2 Nuclear and cytosolic sirtuins involvement in metabolism of cancer and inflammatory cells
10.2.1 SIRT1
10.2.2 SIRT2
10.2.3 SIRT6
10.2.4 SIRT7
10.3 Mitochondrial sirtuins
10.3.1 SIRT3
10.3.2 SIRT4
10.3.3 SIRT5
10.4 Sirtuins indeed link metabolism, inflammation, and cancer?
10.5 Conclusions and perspectives
References
Chapter-11---Sirtuins-and-cellular-meta_2021_Sirtuin-Biology-in-Cancer-and-M
11 Sirtuins and cellular metabolism in cancers
11.1 The metabolic characteristics of cancers
11.1.1 Glucose metabolism in cancers
11.1.2 Lipometabolism in cancers
11.1.3 Other kinds of metabolism in cancers
11.2 The regulatory modes of sirtuins in controlling cellular metabolism
11.3 Direct epigenetic control of cellular metabolism by sirtuins
11.3.1 Direct epigenetic control of glucometabolism by sirtuins
11.3.2 Direct epigenetic control of lipometabolism by sirtuins
11.3.3 Direct epigenetic control of amino acid metabolism by sirtuins
11.4 Direct posttranslational control of cellular metabolism by sirtuins
11.4.1 Direct posttranslational control of glycolytic enzymes and transporters by sirtuins
11.4.2 Direct posttranslational control of OXPHOS by sirtuins
11.4.3 Direct posttranslational control of lipometabolism by sirtuins
11.4.4 Direct posttranslational control of amino acid metabolism by sirtuins
11.5 Indirect control of cellular metabolism by sirtuins
11.5.1 Indirect control of glycolysis by sirtuins
11.5.1.1 HIF-1/2
11.5.1.2 c-Myc
11.5.1.3 LKB1-AMPK
11.5.1.4 p53
11.5.1.5 Other
11.5.2 Indirect control of OXPHOS by sirtuins
11.5.2.1 PGC-1α
11.5.2.2 MnSOD
11.5.2.3 Drp1
11.5.2.4 GABPα/GABPβ complex
11.5.3 Indirect control of lipometabolism by sirtuins
11.5.3.1 PPARα/γ and PGC-1α
11.5.3.2 SREBP family
11.5.3.3 TR4/TAK1
11.5.3.4 PI3K-Akt
11.5.3.5 LKB1
11.5.4 Indirect control of amino acid metabolism by sirtuins
11.6 Conclusions
References
Chapter-12---Dual-role-of-sirtuins_2021_Sirtuin-Biology-in-Cancer-and-Metabo
12 Dual role of sirtuins in cancer
12.1 Introduction
12.2 Sirtuins and cancer metabolism
12.3 Sirtuins and oxidative damage
12.4 Sirtuins, genomic stability, and DNA repair
12.5 Sirtuins and metastasis
12.6 Sirtuins and cancer stem cells
12.7 Sirtuins and chemoresistance
12.8 Sirtuins: tumor suppressors or promoters?
References
Chapter-13---Sirtuin-signaling-in-hemat_2021_Sirtuin-Biology-in-Cancer-and-M
13 Sirtuin signaling in hematologic malignancies
Abbreviations
13.1 Introduction
13.2 Hematologic malignancies
13.2.1 The many facets of SIRT1 in cancer biology
13.2.2 Oncogenic roles of SIRT1
13.2.3 Tumor-suppressive roles of SIRT1
13.2.4 SIRT1 in hematologic malignancies
13.2.5 Closing thoughts on SIRT1
13.2.6 SIRT2 regulates genomic stability
13.2.7 SIRT3, the major mitochondrial deacetylase
13.2.8 The elusive SIRT4 regulates glutamine metabolism
13.2.9 SIRT5: the oncogenic desuccinylase
13.2.10 SIRT6 and the age-old Warburg effect
13.2.11 SIRT7 is an oncogene that promotes ribosome biogenesis and DNA repair
13.3 Sirtuins regulate pathways important for hematologic malignancies
13.3.1 MYC-driven hematologic malignancies
13.3.2 Sirtuins and the BCL-2 family of proteins
13.3.3 Sirtuins regulate NF-κB signaling
13.3.4 CD38, a major NADase, affects sirtuin activity
13.4 Therapeutic opportunities
13.5 Conclusions
References
Chapter-14---Impacts-of-sirtuin1-and-sirtu_2021_Sirtuin-Biology-in-Cancer-an
14 Impacts of sirtuin1 and sirtuin3 on oral carcinogenesis
14.1 Introduction
14.2 Overview of sirtuins
14.2.1 Sirtuin1
14.2.2 Sirtuin3
14.3 Involvement of sirtuins in oral cancer
14.3.1 Sirtuin1 and oral cancer
14.3.2 Sirtuin3 and oral cancer
14.4 Potential therapeutic implications of sirtuins in oral cancer
14.5 Concluding remarks
References
Index_2021_Sirtuin-Biology-in-Cancer-and-Metabolic-Disease
Index