Glycosignals in Cancer: Molecular Assembly and Recognition

Contents
Part I: Search for Novel Tumor Epitopes Related to Carbohydrates
	The Ganglioside Structures: Chemistry and Biochemistry
		1 Gangliosides
		2 Ganglioside Chemical Structure
			2.1 The Ganglioside Oligosaccharide Chain
			2.2 The Ganglioside Ceramide Structures
		3 Physicochemistry of Ganglioside
		4 Biochemistry of Gangliosides
			4.1 The De Novo Biosynthesis of Gangliosides
			4.2 The Structural Modifications at the Cell Surface
			4.3 Ganglioside Catabolism
			4.4 Ganglioside Intracellular Trafficking
		References
	Fucosylated Proteins as Cancer Biomarkers
		1 Introduction
			1.1 Fucosylated Haptoglobin Is a Novel Glycan Biomarker for Cancer and Inflammatory Diseases
		2 Core Fucosylation Is an Apical Sorting Signal
		3 Development of More Convenient Assays to Evaluate Aberrant Glycosylation of PSA
		4 Novel Pathophysiology of Disease-Associated Glycosylation Explored with Next-Generation Antibodies
		5 Closing
		References
Part II: Assembly of Glycoconjugates
	Substantial Basis for Glyco-Assembly: Siglec7 and Synthetic Sialylpolymers
		1 Introduction
		2 Ligand-Binding Site of Siglec7
		3 Interaction Between Siglec7 and Synthetic Glycans
		4 Interaction Between Siglec7 and Synthetic Glycopolymers
		5 Natural Ligands for Siglec7
		6 Future Perspective
		References
	Role of Sialyl-Tn Antigen in Cancer Metastasis
		1 Introduction
		2 Biogenesis of sTn Antigen
		3 Hypoxia-Induced sTn Antigen in Tumor Microenvironments
		4 sTn Antigen in Intratumoral Immune Modulation
		5 sTn Antigen in Epithelial-Mesenchymal Transition (EMT)
		6 sTn Antigen Expression and Integrin-Mediated Tumor Invasion
		7 sTn Antigen Expression and Cancer Stem Cells
		8 Conclusion and Future Perspectives
		References
	Insights into the Role of Chondroitin Sulfate in Cancer
		1 Structure and Biosynthesis of CS
		2 Binding Partners of CS: Soluble Factors
			2.1 WNT Family Members
			2.2 Hedgehog
			2.3 Midkine and Pleiotrophin
			2.4 Other Growth Factors
		3 Binding Partners of CS: Membrane-Bound Type Proteins
			3.1 Cadherin Family
			3.2 Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR1)
			3.3 Toll-Like Receptors
		4 Future Perspectives
		References
Part III: Signaling Pathways Modulated by Glycosylation
	Significance of FUT8 in Pancreatic Cancer and Others
		1 Introduction
		2 Biological Functions and Implications of FUT8
		3 High Expression of FUT8 in Cancer
			3.1 Core-Fucosylated Proteins as Tumor Diagnostic Biomarkers
			3.2 Roles of Core Fucosylation in Cell Adhesion and Cell Migration
			3.3 Roles of FUT8 in Cellular Signaling
			3.4 Roles of FUT8 in TGF-β-Induced EMT
		4 Core Fucosylation Regulates the Stability of Glycoproteins Expressed on the Cell Surface
		5 Glycosylation in Cancer Stem Cells
			5.1 FUT8 Regulates Cancer Stemness
			5.2 FUT8 Increases Multidrug Resistance
		6 Conclusion and Perspectives
		References
	Effects of Bullfrog Sialic Acid-Binding Lectin in Cancer Cells
		1 Introduction
		2 Discovery of cSBL as a Lectin
			2.1 Lectins
			2.2 Sialic Acid-Binding Lectin from Rana Catesbeiana Oocytes
		3 cSBL as an RNase
		4 cSBL as an Antitumor RNase
			4.1 Cytotoxic RNases: Evasion of RNase Inhibitors
			4.2 Antitumor RNases
				Onconase
				BS-RNase
				PE5
			4.3 cSBL
			4.4 Benefits of Antitumor RNase in Cancer Treatment
		5 Antitumor Mechanism of cSBL
			5.1 cSBL-Induced Apoptosis
			5.2 In Vivo Antitumor Activity of cSBL
			5.3 Cancer Selectivity
			5.4 Effect of cSBL in Cancer-Related Molecules
			5.5 Synergistic Effects with Other Drugs
		6 Conclusions and Future Problems
		References
Part IV: Interaction Between Carbohydrate and Carbohydrate-Recognizing Molecules
	Opposite Functions of Mono- and Disialylated Glycosphingo-Lipids on the Membrane of Cancer Cells
		1 Biological Functions of Glycosphingolipids Have Been Further Understood Due to Glycoengineering
		2 Cancer-Associated Glycolipids Often Increase Malignant Properties
		3 Membrane Microdomains GEM/Rafts as Platforms of Signal Transduction
		4 Disialyl Glycosphingolipids Generally Enhance Malignant Phenotypes and Signals in Cancer
		5 Monosialyl Glycosphingolipids Often Suppress Cancer Phenotypes and Signals in Animal Cancer Cells
		6 GM1/GD1b Synthase and Caveolin-1 Suppressed Malignant Phenotypes of Human Cancers
		7 A Novel Approach to Elucidate Mechanisms for Functioning of Cancer-Associated Gangliosides
		8 trans-Interaction of Glycosphingolipids with Their Ligand Molecules Also Affects the Nature of Cells on Both Sides
		9 Application of Signal Studies for Novel Cancer Treatment
		10 Conclusion
		References
	Tumor Progression through Interaction of Mucins with Lectins and Subsequent Signal Transduction
		1 Introduction
			1.1 General
			1.2 Mucin Family
			1.3 Expression of Tumor-Associated Carbohydrate Antigens Due to Aberrant Glycosylation
			1.4 Lectins
		2 Mucin-Mediated Tumor Progression
			2.1 Expression of MUC1
			2.2 Structure of MUC1
			2.3 Growth Factor Receptor-Mediated Phosphorylation of MUC1 and Subsequent Signaling
			2.4 MUC1-Mediated Signaling Through the Binding of Galectin-3 to MUC1
				Binding of Galectin-3 to MUC1
				Enhanced Phosphorylation of ERK1/2 and Akt and Tumor Progression
				Enhanced Recruitment of β-Catenin to MUC1 on Treatment with Galectin-3
			2.5 MUC1-Mediated Induction of Urokinase Type Plasminogen Activator (uPA)
				Correlated Expression of uPA with MUC1
				Formation of the MUC1-CD/NF-κB p65 Complex and Translocation of the Complex to the Nucleus
				Recruitment of the MUC1-CD/NF-κB p65 Complex to the uPA Promoter
				Enhancement of uPA Transcriptional Activity Through Binding of the MUC1-CD/NF-κB p65 Complex to the uPA Promoter
				MUC1-Dependent Cell Invasion Through Elevation of uPA Expression
			2.6 MUC1-Mediated Induction of Trophoblast Cell Surface Antigen 2 (Trop-2)
				MUC1-Dependent Expression of Trop-2
				Involvement of Transcriptional Factor Sp1 in Trop-2 Expression
				Induction of Trop-2 Through the Binding of Galectin-3 to MUC1
				Enhancement of Cell Motility Through Trop-2 Phosphorylation
			2.7 MUC1-Mediated Signaling Triggered by Ligation of Siglec-9
				Binding of Soluble Siglec-9 (sSiglec-9) to MUC1
				MUC1-Mediated Signaling Triggered by Binding of sSiglec-9
				MUC1-Mediated Signaling Triggered by Membrane- Bound Siglec-9
				Downmodulation of β-Catenin Phosphorylation and Enhanced Nuclear Transport of β-Catenin
			2.8 MUC4-Mediated Tumor Progression (Bafna et al. 2010; Kozloski et al. 2010; Hanson and Hollingsworth 2016)
			2.9 MUC16-Mediated Tumor Progression (Haridas et al. 2014; Hanson and Hollingsworth 2016)
		3 Lectin-Receptor-Mediated Immune Regulation
			3.1 DC-SIGN-Mediated Immune Regulation (RodrÍguez et al. 2018)
			3.2 MGL-Mediated Immune Regulation (van Vliet et al. 2005, 2008)
			3.3 Siglec-Mediated Immune Regulation (Adams et al. 2018; van de Wall et al. 2020)
				Siglec-9-Mediated Immune Regulation
		References
Part V: Clinical Trials Targeting Glycosignals
	Immunotherapy of Neuroblastoma Targeting GD2 and Beyond
		1 Introduction
		2 Antibody Therapies
			2.1 Murine Anti-GD2 Antibodies
			2.2 Chimeric Anti-GD2 Monoclonal Antibody
			2.3 Humanized Anti-GD2 Antibody
			2.4 Cytokine-Conjugated GD2-Specific Antibodies
			2.5 Bispecific Antibody
		3 Adoptive Cellular Therapies
		4 Cancer Vaccine
			4.1 Racotumomab Vaccine
			4.2 GD2 Vaccines
			4.3 GD2 Mimotope
			4.4 Anti-GD2 Idiotype Monoclonal Antibody
		5 O-Acetyl GD2-Specific Antibody
		6 Immune Checkpoint Inhibitors
		7 Conclusions
		References