Investigating the Role of SPY1 in Mediating Senescence in Glioblastoma

Glioblastoma (GBM) is a highly aggressive malignant brain tumour. The heterogeneity of GBM renders it resistant to standard-of-care treatment and contributes to tumour recurrence. An emerging area of research in the study of GBM explores cellular senescence, a prolonged state of cell cycle arrest. Spy1, a protein elevated in glioblastomas, overrides cell-cycle checkpoints and avoids conditions that would normally cause cell cycle arrest. This leads to increased and uncontrolled cell proliferation. Thus, Spy1 may be involved in GBM tumour formation by helping cancerous cells evade senescence. To investigate Spy1’s role in mediating senescence, Spy1 will first be knocked down in GBM cell lines. Senescent markers will be evaluated through staining and quantifying senescent cells, alongside analyzing the transcriptional expression of these markers. These assessments will be replicated in Spy1-knockdown GBM cell lines subjected to temozolomide, the conventional treatment for GBM. Finally, senolytic drugs, which target senescent cells, will be administered to these cell lines, and the levels of cell death will be compared between the Spy1 knockdown and control conditions. This project will contribute to the understanding of Spy1’s involvement in GBM, potentially advancing the progress of personalized therapies designed to prevent the initiation and advancement of GBM.