ORCID
- Michael Jones: 0000-0003-3013-1071
Abstract
Bladder cancer is the most common malignancy of the urinary tract. However, bladder cancer is a highly heterogenous disease and our understanding of the mechanisms that drive disease progression remain ill-defined. Additionally, a limited range of therapeutics and the dismal prognosis of patients with advanced disease highlights a need for better understanding of the mechanisms that drive bladder cancer progression, in order to identify new avenues for therapy. The extracellular matrix (ECM) represents a key component of the tumour microenvironment whose biochemical and mechanical characteristics contribute to all the hallmarks of cancer. However, the role of the ECM in bladder cancer is yet to be fully explored. In this thesis, a newly identified role of the matricellular ECM protein vitronectin was discovered, responsible for regulating bladder cancer cell proliferation through integrin αVβ5 mediated mechanisms which contributed to loss of p27 and rapid progression through the cell cycle. Although deregulation of the cell cycle underlies the aberrant cell proliferation that characterises bladder cancer, a novel role of the master cell cycle regulator CDK1 was also identified, responsible for regulating bladder cancer cell invasion independent of its cell cycle activities. This data highlights previously unexplored mechanisms demonstrating a link between cell cycle regulation and adhesion signalling in regulating both bladder cancer cell proliferation and invasion. These mechanisms highlight new avenues that could provide targets for potential therapeutics which may prove successful in treating bladder cancer and reducing disease morbidity.
Awarding Institution(s)
University of Plymouth
Supervisor
Matt Jones, Oliver Hanemann, Peter Sankey
Keywords
Cell Cycle, Extracellular Matrix, Cancer Cell Biology, Bladder Cancer
Document Type
Thesis
Publication Date
2025
Embargo Period
2025-09-09
Deposit Date
September 2025
Additional Links
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License
Recommended Citation
Jones, M. (2025) Links Between Adhesion Signalling and Cell Cycle Regulation in Bladder Cancer Cells. Thesis. University of Plymouth. Available at: https://doi.org/10.24382/at0e-pt82
