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