The unfolded protein response in glioblastoma stem cells: towards new targets for therapy

The aim of this thesis was to investigate ER stress/ UPR signalling in GSCs and explore its potential as a target for therapy in GBM. The importance of the UPR in contributing to acute ER stress-induced cytotoxicity was examined, including effects on the self-renewal potential of GSCs and the underlying molecular mechanisms were elucidated. For this, previously in our lab generated and characterized patient-derived GSC-enriched GBM neurosphere models were employed. A novel noncanonical mechanism for PERK was identified that regulates differentiation and stemness in GSCs. We conclude that ER stress-inducing therapies and PERK modulation may provide promising therapeutic approaches in GBM.

Dissertation: http://hdl.handle.net/11370/c8491508-e8d3-4b2e-9286-bb74df34f8aa