Cancer Cell Signalling

List of contributors ix
Acknowledgements xi
Introduction xiii
About the companion website xvi
1 Epidermal growth factor receptor family 1
Amanda Harvey
1.1 ErbB receptors and their structure 1
1.2 ErbB ligands 2
1.3 Downstream signalling molecules and events 5
1.4 Signalling regulation 8
1.5 Dysregulation of signalling in cancer 10
1.6 Therapeutic opportunities 13
References 17
2 Insulin and the insulin-like growth factor (IGF) family 25
Maria Thorpe, Erald Shehu and Amanda Harvey
2.1 Receptors 25
2.2 Ligands 28
2.3 Downstream signalling molecules and events 30
2.4 Dysregulation of signalling in cancer 32
2.5 Therapeutic opportunities 34
References 37
3 Transforming growth factor-ß receptor signalling 45
Gudrun Stenbeck
3.1 TGFß receptors 45
3.2 Ligands 48
3.3 Downstream signalling molecules and events 49
3.4 Signalling regulation 53
3.5 Dysregulation of signalling in cancer 56
3.6 Therapeutic opportunities 58
References 60
4 Wnt signalling 67
David Tree
4.1 Introduction and overview 67
4.2 The ligands: Wnt proteins, their modification and secretion 69
4.3 The receptors: Frizzleds and LRPs, multiple receptors and combinations 70
4.4 Regulation of signalling 71
4.5 When good signalling goes bad: Wnt signalling in diseases 79
4.6 Taming the beast: drugs and small molecule inhibitors targeting Wnt signalling 80
4.7 Conclusion and perspectives 81
References 82
5 Mammalian target of rapamycin (mTOR) signalling 93
Maria Thorpe and Emmanouil Karteris
5.1 Discovery of mTOR 93
5.2 mTOR complexes 94
5.3 mTOR dysregulation in disease 99
5.4 Therapeutic opportunities 104
References 107
6 c-Met receptor signalling 115
Stephen Hiscox
6.1 Historical context - identification of the MET gene 115
6.2 c-Met expression, activation and signal transduction 119
6.3 Physiological roles of c-Met 121
6.4 c-Met and cancer 123
6.5 c-Met as a potential therapeutic target in malignancy 128
6.6 Summary 130
References 130
7 Vascular endothelial growth factor and its receptor family 139
Katarzyna Leszczynska, Christopher Hillyar and Ester M. Hammond
7.1 VEGF receptors 139
7.2 Ligands 140
7.3 Downstream signalling molecules and events 143
7.4 Signalling regulation 150
7.5 Dysregulation of signalling in cancer 152
7.6 Therapeutic opportunities 153
References 158
8 Progesterone receptor signalling in breast cancer models 171
Andrea R. Daniel, Todd P. Knutson, Christy R. Hagan and Carol A. Lange
8.1 Progesterone receptor function 172
8.2 Model systems: context for studying PR biochemistry 174
8.3 Progesterone receptor signalling 175
8.4 Regulation of signalling 176
8.5 Tissue specific PR actions (breast versus reproductive tract) 181
8.6 Progesterone receptor and cancer 183
8.7 Summary 183
References 184
9 Signalling cross-talk 193
Amanda Harvey
9.1 Introduction 193
9.2 Examples of cross-talk 195
9.3 Convergence of signalling at downstream foci 197
9.4 Common signalling components 198
9.5 Compensatory signalling 202
9.6 Summary 203
References 203
Index 207