Identification of functional sites of mechanotransduction on syndecan-4 for therapeutic targeting in pancreatic cancer

Markus Hahn

More than 600 people are diagnosed with pancreatic cancer each year in Ireland, equivalent to 12 per week. Pancreatic cancer has one of the lowest survival rates of all cancers with less than 1-in-10 surviving 5-years beyond diagnosis. Progress toward improving survival has been slow and the number of people diagnosed increases every year.

Pancreatic cancer is resistant to conventional treatment options including chemotherapy, radiotherapy, and immunotherapy. One of the reasons for this treatment resistance is that pancreatic cancer tumours contain a substantial quantity of collagen. This makes these tumours hard and stiff. Tumour cells sense this stiffness, which makes them more likely to spread within the body.

One of the ways cells interact with their surrounding tissue is through a molecule called syndecan-4. All cells have syndecan-4 on their surface, but pancreatic cancer cells express much more syndecan-4 than is typical. Removal of syndecan-4 from cancer cells makes them less mobile, which could prevent them from spreading. This project will assess which part of the syndecan-4 protein is responsible for its function in pancreatic cancer. This will provide for the development of drugs targeting the function of syndecan-4 which could provide a new treatment for pancreatic cancer.