Identification of Novel CDK1 Regulators and Substrates That Mediate Bladder Cancer Cell Invasion

Identifying new mechanisms that drive bladder cancer cells to invade their surrounding muscle tissue holds the key to discovering drugs for treating muscle-invasive bladder cancer and improving patient outcomes. We have already identified a new regulator of invasion, Cyclin-dependent kinase 1 (CDK1), but to generate drugs that will specifically target bladder cancer cells, it is vital to pinpoint the proteins that switch on CDK1 or are activated by CDK1 in invasive bladder cancer. This project aims to achieve this, defining new pathways that can be targeted therapeutically to prevent tissue invasion and metastasis of bladder cancer cells.

Background: Treatment options for bladder cancer have changed little in the last 40 years and our understanding of what drives bladder cancer progression is poor. If cancer cells have moved away from the bladder lining and invaded into the bladder muscle and beyond then the survival rate is poor (36% 1 year survival). To treat this invasive type of bladder cancer, either the entire bladder is removed, or the patient receives radiotherapy. There are some drugs that have recently shown to have an effect in a specific subset of patients, but overall there are no drugs that specifically target invasive bladder cancer. This is due to a lack of research into the mechanisms that promote bladder cancer cell invasion, especially in comparison to other cancer types. We have identified cyclin-dependent kinase-1 (CDK1) as a novel regulator of bladder cancer cell invasion and have shown that it is expressed in higher levels in invasive bladder cancer cells compared to non-invasive cancer cells and normal cells. However, CDK1 is found in all cells in the body and works to promote cell division so in this study we aim to find proteins that regulate CDK1, or proteins that are regulated by CDK1, specifically in invasive bladder cancer cells.

Patient benefit: Achieving this will identify novel therapeutic targets for invasive bladder cancer treatment and describe potential new diagnostic tools. Overall, the findings from this study will increase our understanding of how bladder cancer cells invade their surrounding environment and subsequently metastasize.

Project Lead:

Dr Matthew Jones, Derriford Research Facility, Peninsula Medical School, University of Plymouth.

Read about the other 2024 IOPP grant-awarded projects.