Proteostatic regulation of Glioblastoma stemness

Glioblastoma is the most aggressive type of brain cancer in adults. There is no cure, and most patients die within 15-18 months after diagnosis, even with treatment. Developing effective therapies against glioblastoma is very difficult, because these cancers are made up of a very diverse mixture of different cancer cells. We have found that a type of glioblastoma cells that is more aggressive than other cells from this cancer also contains more proteins than less aggressive glioblastoma cells. We think this allows more aggressive glioblastoma cells to grow quicker which helps these cells to be more aggressive and regrow into new tumours after treatment.

Our project will investigate differences in proteins between more aggressive and less aggressive glioblastoma cells to find new ways for treating glioblastoma by stopping more aggressive cells from growing. We want to understand how protein production is conducted in each glioblastoma cell type, and we will combine different ways of investigating proteins inside glioblastoma cells. This will allow us to study not only the type of proteins being made, but also how they interact with one another and how they are broken down. As part of our project, we will investigate the protein HECTD1 since it controls the factory which makes proteins, called the ribosome. We will test whether HECTD1 helps more aggressive glioblastoma cells to make more protein and therefore helps glioblastomas to grow back after therapy. This may help find new ways of treating glioblastoma. Finally, we are using a new type of microscope for measuring protein amounts inside glioblastoma cell types and this is exciting because this technology has the potential to readily identify more aggressive glioblastoma cells, with increased sensitivity and quicker than ever before. We will test this in human patient material to evaluate its diagnostic/prognostic value. This new technology could help other scientists and clinicians in the future by making it easier to identify and study more aggressive cancer cells.