...................................................................................................................................... i Dedication .................................................................................................................................. ii Table of contents ...................................................................................................................... iii List of figures ............................................................................................................................. v Acknowledgements ................................................................................................................... vi List of abbreviations ................................................................................................................ vii Chapter 1: Introduction .............................................................................................................. 1 1.1 Cancer: an overview ......................................................................................................... 1 1.1.1 Ovarian cancer ........................................................................................................... 1 1.1.2 Colorectal Cancer ...................................................................................................... 2 1.2 WWOX: a bona fide tumour suppressor gene ................................................................ 2 1.2.1 The role of WWOX in ovarian cancer ....................................................................... 3 1.3 The endoplasmic reticulum and ER stress ....................................................................... 3 1.4 ER stress and the unfolded protein response .................................................................... 4 1.4.1 Mechanism of the UPR.............................................................................................. 4 1.4.2 The apoptotic arm of the UPR ................................................................................... 6 1.5 The UPR and cancer development ................................................................................... 7 1.6 ER stress and chemotherapy ............................................................................................ 8 1.6.1 Paclitaxel ................................................................................................................... 8 1.7 Aims ................................................................................................................................. 9 1.7.1 Targeting ER stress in order to inhibit paclitaxel chemotherapy response ............... 9 1.7.2 Characterizing the activation of ER stress by paclitaxel in different cancer cell lines ............................................................................................................................................ 9 Chapter 2: Materials and methods ........................................................................................... 11 2.1 Cell culture ..................................................................................................................... 11 2.1.1 Basic maintenance of cell lines ............................................................................... 11 2.1.2 Passaging of cell lines .............................................................................................. 11 2.1.3 Freezing and recovery of cell lines .......................................................................... 11 2.2 Cell survival assays ........................................................................................................ 11