Chatterjee / Kashfi Cell Signaling & Molecular Targets in Cancer

1. Auflage 2011
ISBN: 978-1-4614-0730-0
Verlag: Springer
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 328 Seiten

This book provides an overview of critical components of cell signaling machinery and its role in epithelial morphogenesis, proliferation, invasions and angiogenesis in human cancer and discusses novel types of protein kinase pathways.

Autoren/Hrsg.

Chatterjee, Malay

Kashfi, Khosrow

Inhaltsverzeichnis

1;Cell Signaling & MolecularTargets in Cancer;3
1.1;Acknowledgement;5
1.2;Contents;7
1.3;Contributors;9
1.4;Chapter 1: GRB2 Signaling as a Molecular Target for Cancer;13
1.4.1;Introduction;13
1.4.1.1;Adaptor Proteins in Cell Signaling;13
1.4.1.2;The Grb Family;14
1.4.2;The Adaptor Protein GRB2;15
1.4.2.1;Grb2 in Cell Signaling;15
1.4.2.2;Grb2 and Cancer;17
1.4.2.3;Involvement of Grb2 in Invasion and Metastasis;18
1.4.2.3.1;Grb2 Involvement in the Early Phases of the Metastatic Cascade;19
1.4.2.3.2;Role of Grb2 in Angiogenesis and Dissemination;24
1.4.2.4;Development of Grb2 Inhibitors as Anticancer Drugs;26
1.4.3;Conclusions and Prospectives;29
1.4.4;References;30
1.5;Chapter 2: Human Arylamine N -acetyltransferase 1: From Drug Metabolism to Drug Target;35
1.5.1;Introduction;35
1.5.2;Human NAT1 Gene Structure and Polymorphism;37
1.5.3;Human NAT1 Protein Structure;40
1.5.4;Animal Models to Understand NAT1 Functions;41
1.5.5;Possible Relevance of NAT1 in Cancer;42
1.5.6;NAT1 as a Drug Target in Cancer;43
1.5.7;References;45
1.6;Chapter 3: Targeting Argininosuccinate Synthetase in Cancer Therapy;48
1.6.1;Introduction;48
1.6.2;Background;48
1.6.3;Why Arginine Deprivation Is Important;49
1.6.3.1;Preclinical Antitumor Activity of ADI-PEG20;51
1.6.3.2;ASS Expression and Arginine Deprivation in Melanoma;51
1.6.3.3;Arginine Deprivation in Hepatocellular Carcinoma;52
1.6.3.4;Arginine Deprivation in Other Tumor Cell Types;53
1.6.4;How Arginine Deprivation Affects Growth and Apoptotic Signaling;53
1.6.4.1;Arginine Deprivation Affects mTOR Signaling;53
1.6.4.2;Arginine Deprivation on RAF/MEK/ERK1/2 Signaling;54
1.6.4.3;Arginine Deprivation Leads to Autophagy in ASS( ) Cells;54
1.6.5;How Arginine Deprivation Induces Cell Death in ASS( ) Melanoma Cells;55
1.6.5.1;ASS Expression and Cisplatin Resistance;56
1.6.5.2;Other Effects of Arginine Deprivation;57
1.6.5.3;Clinical Trials with ADI-PEG20;58
1.6.6;Concluding Remarks and Future Direction;59
1.6.7;References;60
1.7;Chapter 4: Parathyroid Hormone–Related Peptide Signaling in Cancer*;63
1.7.1;Introduction;63
1.7.2;PTHrP Gene Structure and Regulation;64
1.7.3;Cancer Cell Growth;68
1.7.3.1;Regulation of ERK1/2 by G s;73
1.7.3.2;Regulation of ERK1/2 by G a q;75
1.7.4;Apoptosis;77
1.7.5;Invasiveness and Integrins;79
1.7.6;PTHRP and Bone Metastases;83
1.7.7;References;88
1.8;Chapter 5: Signalling Molecules as Selective Targets for Therapeutic Strategies in Multiple Myeloma;96
1.8.1;Epidemiology and Aetiology;96
1.8.2;Pathobiology of MM;96
1.8.3;Targeting Growth- and Survival-Promoting Signalling Cascades in MM PCs;98
1.8.3.1;The IL-6 Signalling System;98
1.8.3.2;IGF-I Signalling;101
1.8.3.3;The NF- k B Pathway;101
1.8.3.4;The PI3K/AKT Pathway;102
1.8.3.5;Bcl-2 Protein Family;102
1.8.3.6;Farnesyltransferase Inhibitors (FTIs);103
1.8.4;TRAIL;104
1.8.5;Targeting Protein Maturation, Degradation and Acetylation;104
1.8.5.1;Hsp90 Inhibitors;104
1.8.5.2;Proteasome Inhibitors;105
1.8.5.2.1;Bortezomib;105
1.8.5.2.2;NPI-0052;106
1.8.5.2.3;Carfilzomib (PR-171);106
1.8.5.3;HDAC Inhibitors;106
1.8.6;Targeting the Myeloma Malignant Bone Marrow Microenvironment;107
1.8.6.1;Immunomodulatory Therapies;107
1.8.6.2;Anti-angiogenic Therapy;108
1.8.6.2.1;VEGF Inhibitors;108
1.8.6.2.2;Fibroblast Growth Factor Receptor 3 (FGFR3) Inhibitors;109
1.8.6.3;Other Signalling Pathways;109
1.8.6.3.1;P38 MAP Kinase Inhibitors;109
1.8.6.3.2;TGF b Inhibitors;109
1.8.7;Summary;110
1.8.8;References;110
1.9;Chapter 6: Role of Bile Acids in Carcinogenesis of Gastrointestinal Tract;118
1.9.1;Introduction;118
1.9.2;Bile Acids and Carcinogenesis;119
1.9.3;Bile Acids and COX-2 Expression in Gastrointestinal Carcinogenesis;120
1.9.4;Bile Acids and Human Gastrointestinal Cancer;121
1.9.4.1;Esophagus;121
1.9.4.1.1;Esophageal Squamous Cell Carcinoma;121
1.9.4.1.2;Barrett’s Epithelium and Esophageal Adenocarcinoma;121
1.9.4.1.3;CDX-2 and Barrett’s Epithelium;122
1.9.4.1.4;COX-2 Expression and Bile Acids in Esophageal Adenocarcinoma;122
1.9.4.2;Stomach;123
1.9.4.2.1;Gastric Carcinogenesis and Duodeno-gastric Reflux;123
1.9.4.2.2;Gastric Carcinogenesis and COX-2;124
1.9.4.3;Colorectal Cancer;125
1.9.4.3.1;Colon Cancer and Bile Acids;125
1.9.4.3.2;Colorectal Cancer and COX-2;126
1.9.5;Bile Acid Receptors and Gastrointestinal Carcinogenesis;127
1.9.5.1;GPCR and EGFR Crosstalk and Carcinogenesis;127
1.9.5.1.1;Bile Acid Receptors and EGFR Transactivation;128
1.9.5.2;Bile Acids as Ligands for GPCR;129
1.9.5.2.1;M 3 Muscarinic Receptor and EGFR Activation;129
1.9.5.2.2;TGR5 and EGFR Transactivation;129
1.9.5.2.3;FXR and Colon Carcinogenesis;130
1.9.6;Conclusions;132
1.9.7;References;132
1.10;Chapter 7: AIB1: A Transcriptional Coactivator Which Integrates Signaling Cross Talk in Cancer Cells;138
1.10.1;Introduction: Cancer Etiology and Signal Transduction;138
1.10.2;The Steroid Receptor Coactivator or p160 Family;140
1.10.3;Role of AIB1 in Physiology;145
1.10.3.1;Role of AIB1 During Development;145
1.10.3.2;Role of AIB1 in Reproductive Tissues;146
1.10.3.3;Role of AIB1 in the Central Nervous System;147
1.10.3.4;Role of AIB1 in Energy Homeostasis;147
1.10.3.5;Role of AIB1 in Other Tissues;148
1.10.4;Overexpression of AIB1 Affects Both Cancer Initiation and Progression;149
1.10.4.1;Evidences from Biopsies and Animal Models;149
1.10.4.2;Mechanisms of AIB1 Oncogenic Activity;152
1.10.4.2.1;Hormone-Dependent Mechanisms: The Steroid Receptor Signaling;152
1.10.4.2.2;Hormone-Independent Mechanisms;154
1.10.4.2.2.1;The IGF/PI3K/AKT Signaling Pathway;154
1.10.4.2.2.2;The ErbB/HER Signaling Pathway;156
1.10.4.2.2.3;The NF-.B Signaling Pathway;156
1.10.4.2.2.4;The Rb/E2F1 Signaling Pathway;157
1.10.4.2.3;Invasiveness Mechanisms;157
1.10.5;Cell Cycle Regulation by AIB1;159
1.10.6;IGF-I Is a Mediator of AIB1 Signaling;161
1.10.7;Overexpression of AIB1 and HER2/NEU Correlates with Tamoxifen Resistance;163
1.10.8;Predictive and Prognostic Factors: Targeting AIB1 in Cancer Therapy;165
1.10.9;References;168
1.11;Chapter 8: Rational Design of DNA Anticancer Agent That Targets Signal Transducer and Activator of Transcription 3 (Stat3) for Cancer Therapy;176
1.11.1;Introduction;176
1.11.2;Developed Inhibitors of Stat3 Signaling;178
1.11.2.1;Organic Compounds;178
1.11.2.2;Peptide Inhibitors;178
1.11.2.3;DNA Inhibitors;179
1.11.2.4;Protein Inhibitors;179
1.11.3;G-Quartet Oligodeoxynucleotides (GQ-ODNs) as a Potential Anticancer Drug;179
1.11.4;Rational Design of G-Rich ODNs That Target Stat3 Signaling;181
1.11.4.1;Structure-Based Drug Design;181
1.11.4.2;GQ-ODN T40214 Selectively Inhibiting Stat3 Activation;181
1.11.4.3;An Effective Drug Delivery System for GQ-ODNs;183
1.11.4.4;The Drug Activity of GQ-ODN Was Greatly Increased by the Effective Delivery;186
1.11.4.4.1;Drug Activity in Cancer Cells;186
1.11.4.4.2;Drug Delivery and Activity In Vivo;186
1.11.4.5;T40214 Suppresses the Growth of Prostate Tumor Xenografts in Nude Mice;188
1.11.4.5.1;Prostate Cancer Therapy;188
1.11.4.5.2;Other Solid Tumor Therapies;188
1.11.4.6;The Mechanism of GQ-ODN T40214 as a Potent Anticancer Agent;191
1.11.4.6.1;The Mechanism of T40214 Suppression of Tumor Growth;191
1.11.4.6.2;T40214 as an Anticancer Agent Targeting Stat3 Signaling for Cancer Therapy;191
1.11.4.7;Toxicity of GQ-ODN T40214/PEI Complex;194
1.11.4.7.1;Toxicity of GQ-ODNs: G-Quartet ODNs Are Low-Toxicity Agents;194
1.11.4.7.2;Toxicity of PEI;194
1.11.4.7.3;T40214/PEI Complex Shows No Toxicity;194
1.11.5;Summary;196
1.11.5.1;Stat3: An Important Target in Cancer Therapy;196
1.11.5.2;Potential Impact of T40214 on Cancer Therapy;196
1.11.6;References;197
1.12;Chapter 9: Estrogen Receptor Signaling in Lung Cancer;200
1.12.1;Introduction;200
1.12.2;Estrogen Receptors Mediating Estrogen Action;201
1.12.3;Lung: An Estrogen-Responsive Tissue;203
1.12.4;Effects of Endogenous and Exogenous Estrogens (Hormone Replacement Therapy) on Lung Cancer Risk and Lung Cancer Outcomes;204
1.12.5;Preclinical Studies Indicating that Estrogen Supports the Development or Growth of NSCLC;205
1.12.6;Evaluation of the Functionality of the Classical Genomic Estrogen-Signaling Pathway in NSCLC Cells;206
1.12.7;Membrane-Initiated Steroid Signaling (MISS) in Lung Epithelial Cells and NSCLC;206
1.12.8;Estrogen Receptors and Mitochondria;207
1.12.9;Estrogen Receptors Expressed in NSCLC Cells and Human Primary Lung Tumors;209
1.12.10;Using Subtype Selective Ligands to Assess the Relative Contributions of ER b and ER a in NSCLC Cell Lines;210
1.12.11;E2 Cooperates with Growth Factor Receptor Signaling to Increase the Growth of NSCLC Cells;211
1.12.12;Aromatase;213
1.12.13;Summary and Future Directions;215
1.12.14;References;215
1.13;Chapter 10: Microparticle Dissemination of Biological Activities: Implications for Cancer Biology;220
1.13.1;Introduction;220
1.13.2;Cell-Derived Microparticles;221
1.13.2.1;Mechanism of MP Generation, Release, and Action;221
1.13.2.2;Stimuli Triggering MP Generation;222
1.13.2.3;Measurement of MP;224
1.13.3;Role of Cell-Derived MPS in Tumor Growth, Angiogenesis, and Metastasis;225
1.13.3.1;Tumor Progression and Metastasis;225
1.13.3.1.1;Tumor Cell-Derived MPs (TMPs) and Tumor Growth, Angiogenesis, and Metastasis;225
1.13.3.1.1.1;TMPs and Tumor Invasion and Metastasis;226
1.13.3.1.1.2;TMPs and Tumor-Induced Angiogenesis;227
1.13.3.1.1.3;TMPs and Immune Escape;231
1.13.3.1.1.4;TMPs and Trafficking to Metastatic Foci;232
1.13.3.1.2;Platelet-Derived MP (PMP) and Tumor Growth, Angiogenesis, and Metastasis;234
1.13.4;Tissue Factor-Positive Microparticles and Cancer-Associated Thrombosis;236
1.13.4.1;Cancer-Associated Thrombosis;236
1.13.4.1.1;Tissue Factor in Cancer-Associated Thrombosis;236
1.13.4.1.2;Studies Implicating Tissue Factor-Positive MPs in Cancer-Associated Thrombosis;237
1.13.4.1.3;Tissue Factor-Positive MPs – Cellular Origin and Procoagulant Activity;239
1.13.4.1.4;Protein Disulfide Isomerase – Potential Modulator of TF Activity;240
1.13.4.1.5;Proposed Model for Promotion of Thrombus Development by TF-Expressing MP and Platelet-Derived PDI;243
1.13.5;Conclusion and Future Perspectives;244
1.13.6;References;246
1.14;Chapter 11: Protein Kinase D Signaling in Cancer;253
1.14.1;Introduction;253
1.14.2;Activation of PKD;256
1.14.2.1;Upstream Activators for PKD;256
1.14.2.2;Signaling Mechanisms Regulating PKD Activity;258
1.14.3;Role of PKD in Tumor Cell Proliferation;260
1.14.4;Role of PKD in Tumor Cell Survival Signaling;262
1.14.5;Functions of PKD in Chemoresistance;263
1.14.6;Role of PKD in Tumor Cell Migration and Invasion;264
1.14.7;Regulation of PKD Expression in Cancer;267
1.14.8;PKD as a Regulator of Angiogenesis;268
1.14.9;Perspective;269
1.14.10;References;271
1.15;Chapter 12: Cell Signaling and Cancer: Integrated, Fundamental Approach Involving Electron Transfer, Reactive Oxygen Species, and Antioxidants;280
1.15.1;Introduction;280
1.15.1.1;Tenets of OS Theory;281
1.15.2;Chronology;282
1.15.3;Stages in Carcinogenesis;282
1.15.3.1;Cell Signaling;283
1.15.4;Integrated Approach;284
1.15.4.1;Endogenous Agents;284
1.15.4.2;Exogenous Agents;288
1.15.4.2.1;Metals and Particulates;288
1.15.4.2.2;Ultraviolet (UV) Radiation;289
1.15.4.2.3;Hydrogen Peroxide;289
1.15.4.2.4;Alcohol;290
1.15.4.2.5;Ginkgo Biloba;290
1.15.4.2.6;Curcumin;290
1.15.4.2.7;Endosulfan;290
1.15.4.2.8;Benzene;290
1.15.4.2.9;Polycyclic Aromatic Hydrocarbons (PAHs);291
1.15.4.2.10;Estrogen Quinone;291
1.15.4.3;Antioxidants;291
1.15.4.4;Chemotherapeutic Agents and Preventions;292
1.15.4.4.1;Aminoflavone;292
1.15.4.4.2;Curcumin;293
1.15.4.4.3;Radiation;293
1.15.4.4.4;Nitric Oxide;293
1.15.4.4.5;Resveratrol;293
1.15.4.4.6;Polyphenols;293
1.15.4.4.7;Formaldehyde;294
1.15.4.4.8;Isoobtusilactone (IOA);294
1.15.4.4.9;Genipin;294
1.15.4.4.10;Decursin;294
1.15.4.4.11;Quinoline Quinone;294
1.15.4.4.12;Acacetin;295
1.15.4.4.13;Berberine;295
1.15.4.4.14;PAC-1 and UCS1025A;295
1.15.4.4.15;Selenium;295
1.15.4.4.16;Dialkyl Disulfide (DADS);295
1.15.4.4.17;Onion;296
1.15.4.4.18;SOD;296
1.15.4.4.19;Phytochemicals;296
1.15.5;References;296
1.16;Chapter 13: Targeting Signal Transducer and Activator of Transcription (STAT) for Anticancer Therapy*;305
1.16.1;Introduction;305
1.16.2;Structure and Function of STATs;306
1.16.2.1;STAT Activation–Inactivation Cycle;306
1.16.2.2;STAT Function;307
1.16.2.3;STAT Phosphorylation and Activation;308
1.16.2.4;STAT Serine Phosphorylation and Other STAT Modifications;309
1.16.2.5;Activation of Transcription;309
1.16.2.5.1;Protein Inhibitor of Activated STAT;309
1.16.3;STAT and Tumor Biology;310
1.16.3.1;Overview;310
1.16.3.2;Constitutive Activation of STATs in Cancer;310
1.16.3.3;STATs and Tumor Cell Proliferation and Resistance to Apoptosis;311
1.16.3.4;STATs and Tumor Angiogenesis;312
1.16.3.5;Role of STATs in Evading Immune Surveillance Mechanisms;313
1.16.4;Targeting STATS;314
1.16.4.1;Peptidic Inhibitors and Peptidomimetic Inhibitors;314
1.16.4.2;Small-Molecule Non-peptidic Inhibitors;314
1.16.4.2.1;Inhibitors of STAT DNA Binding Domains;315
1.16.4.2.2;Inhibitors of the N-Terminal Domain;316
1.16.4.2.3;Oligonucleotides Targeting STAT3;317
1.16.4.3;Tyrosine Kinase Inhibitors;318
1.16.4.4;Natural Compounds;318
1.16.4.5;Other Compounds with STAT3 Inhibitory Activity;321
1.16.4.5.1;Activators of STAT Inhibitors;322
1.16.5;Conclusion;322
1.16.6;References;322
1.17;Index;328