International Review of Cell and Molecular Biology (eBook)

Front Cover 1
International Review of Cell and Molecular Biology 2
International Review of Cell and Molecular Biology 3
International Review of Cell and Molecular Biology 
4 
Copyrights 
5 
Contents 6
Contributors 10
Epidermal Growth Factor Signaling in Transformed Cells 12
1. Introduction 13
2. Hallmarks of Transformation 14
2.1 Epithelial–Mesenchymal Transition 15
2.2 Role of EGFR in EMT 18
3. The ErbB/HER Receptor Family in Normal and Transformed Cells 19
3.1 Overview of EGFR Receptors, Ligands, and Signaling 19
3.2 ErbB/HER Family Members in Transformed Cells 21
3.3 EGFR Mutations 21
3.4 EGFR Polymorphism 22
3.5 EGFR Ligands 23
4. EGFR Signaling in Normal and Transformed Cells 24
4.1 Loss of Cell Adhesion and EGFR Signaling 25
4.2 Tumor Microenvironment and EGFR Signaling 26
4.3 Posttranslational Modifications and EGFR Signaling 28
4.4 Epigenetic Influences on EGFR Signaling 28
4.5 MicroRNAs and EGFR 29
4.6 Compartmentalization and Trafficking of EGFR 30
4.7 EGFR Transactivation 31
5. Cross Talk between EGFR Signaling and Other Major Signaling Pathways in Transformed Cells 32
5.1 Mesenchymal Epithelial Transition Factor 32
5.2 Transforming Growth Factor-Beta 33
5.3 Insulin-like Growth Factor 34
5.4 Sonic Hedgehog 34
5.5 Wnt 35
5.6 Notch 35
6. Therapy 36
6.1 EGFR as Target for Cancer Therapy 37
6.2 Anti-EGFR Therapy Approaches 37
6.3 Resistance to EGFR Therapy 39
7. Concluding Remarks 40
Acknowledgments 40
References 40
New Insights into Antimetastatic and Antiangiogenic Effects of Cannabinoids 54
1. Introduction 57
2. Cannabinoids as Systemic Anticancer Drugs 59
2.1 Range of Antitumorigenic Mechanisms of Cannabinoids 59
2.2 Cannabinoids: Clinical Implication as Systemic Anticancer Drugs 60
2.2.1 Case–control studies with Cannabis smokers 60
2.2.2 The endocannabinoid system as tumor-defense mechanism 62
2.2.3 Combinational cancer therapies with cannabinoids 64
2.2.4 Cannabinoids' impact on tumor-immune surveillance 67
2.3 Cannabinoids as Potential Clinical Option to Counteract Tumor Metastasis and Angiogenesis 70
3. Cannabinoids and Tumor Angiogenesis 72
3.1 Angiogenesis in Physiological and Pathophysiological Tissue Development 72
3.2 Cannabinoids' Effects on Tumor Angiogenesis In vivo 86
3.3 Direct Effects of Cannabinoids on Vascular Endothelial Cells 88
3.4 Impact of Cannabinoids on the Release of Angiogenic Factors from Tumor Cells 93
3.5 Cannabinoids and Angiogenesis: A Critical Outlook 95
4. Effects of Cannabinoids on Tumor Cell Metastasis 95
4.1 Impact of Cannabinoids on Tumor Cell Migration 96
4.2 Impact of Cannabinoids on Tumor Cell Invasion 97
4.2.1 Contribution of the endocannabinoid system to tumor cell invasion 101
4.3 Effects of Cannabinoids on Metastasis In vivo 104
4.4 Cannabinoids and Metastasis: A Critical Outlook 107
5. Conclusion 108
References 108
Insight into the Role of Wnt5a-Induced Signaling in Normal and Cancer Cells 128
1. Introduction 129
2. Wnt5a–Ror2 Axis in Developmental Morphogenesis 130
2.1 Planar Cell Polarity 131
2.2 CE Movements 132
2.3 Epithelial–Mesenchymal Interaction 134
3. Roles of Wnt5a–Ror2 Axis in Normal Cell Functions 135
3.1 Cell Polarity 136
3.2 Cell Migration 137
3.3 Gene Expression 139
3.4 Maintenance of Stemness 140
4. Wnt5a–Ror2 and Ror1 Axes in Cancer Cells 142
4.1 Tumor-Progressive Functions 142
4.1.1 Epithelial-to-mesenchymal transition and Wnt5a-Ror2 axis 142
4.1.2 Wnt5a–Ror2 axis in high motility and invasion 143
4.1.3 Wnt5a–Ror2 axis in metastasis 144
4.1.4 Ror1 axis in survival and proliferation of cancer cells 145
4.1.5 Cross talk with different signaling axes 147
4.1.6 Ror1 axis in drug resistance 148
4.2 Tumor-Suppressive Functions of Wnt5a 149
5. Concluding Remarks 149
Acknowledgments 151
References 151
New Insight into Cancer Aneuploidy in Zebrafish 160
1. Introduction 161
2. The Cause of Aneuploidy 162
3. Biological Effects of Aneuploidy 163
3.1 Gene Expression and Dosage Compensation 163
3.2 Impacts on Organism Fitness 164
3.3 Cellular Impacts on Noncancerous Cells 165
3.4 Aneuploidy in Cancer 165
4. Zebrafish as a Cancer Model for Human Cancers 166
4.1 Polyploid Zebrafish 167
4.2 Zebrafish Aneuploid Mutants 168
4.3 Aneuploid Nature of Zebrafish Cancers 169
5. Cancer Driver Genes on Aneuploid Chromosomes 170
5.1 Finding Cancer Driver Genes by Cross-Species Comparisons 170
5.2 Functional Validations of Cancer Driver Genes 173
6. Future Directions 173
Acknowledgments 175
References 175
The Amazing Ubiquitin-Proteasome System: Structural Components and Implication in Aging 182
1. Introduction 184
2. Aging 186
3. The Ubiquitin System 190
3.1 Ub-Conjugating Enzymes 191
3.2 The Fate of the Ubiquitinated Protein 193
3.3 Recycling of Ub 194
4. The Proteasome 195
4.1 20S CP: Structure, Function, and Assembly 195
4.2 19S RP: Structure, Function, and Assembly 198
4.3 Alternative Proteasome Forms 200
4.4 Subcellular Localization and Regulation of the Proteasome 200
4.5 The Endoplasmic Reticulum-Associated Degradation 205
4.6 The Outer Mitochondrial Membrane-Associated Degradation 208
4.7 Cross Talk between the UPS and the other Components of the Cellular Proteostasis Network 209
4.7.1 UPS and the other proteolytic pathways 209
4.7.2 UPS and the network of molecular chaperones 210
4.7.3 UPS and cellular antioxidant responses 211
5. Regulation of the Ub System during Cellular Senescence and In vivo Aging 213
6. Implication of ERAD and OMMAD in Cellular Senescence and In vivo Aging 214
7. Alterations of the Proteasome Functionality during Cellular Senescence and In vivo Aging 215
8. Modulation of the UPS as an Antiaging Approach 219
9. Conclusive Remarks and Perspectives 222
Acknowledgments 223
References 223
Biogenesis and Function of the NGF/TrkA Signaling Endosome 250
1. Introduction 251
2. NGF 253
2.1 Biogenesis 253
2.2 Physiological Importance 254
3. TrkA 254
3.1 Biogenesis and Localization 255
3.2 Signaling 256
4. The Signaling Endosome 257
4.1 Biogenesis 259
4.2 Trafficking 261
4.3 Rab Function 261
5. Concluding Remarks 263
Acknowledgments 264
References 264
Multiple Myeloma as a Model for the Role of Bone Marrow Niches in the Control of Angiogenesis 270
1. Introduction 270
2. EPCs and MSCs 272
3. Vascular Niche 273
4. Osteoblastic Niche 274
5. MM Niche and Angiogenesis 276
6. Targeting Angiogenesis in the MM Niche 280
7. Concluding Remarks 284
Acknowledgments 285
References 285
Index 294