Thesis Defense

“Identification of molecular actors regulated by IRE1 that control protein secretion in glioblastoma cells”

Ketsia BAKAMBAMBA

PhD candidate in UMR INSERM U1242 Oncogenesis Stress Signaling

PROSAC Team

Abstract:

Glioblastoma (GB) is an aggressive and deadly brain tumor with a highly heterogeneous pathophysiology, contributing to its resistance to current therapies. Despite advances in research, the prognosis for GB patients remains poor, highlighting the need for better characterization of the disease and the development of novel therapeutic strategies.
This thesis focuses on the central role of the endoplasmic reticulum (ER) and its stress response, particularly the Unfolded Protein Response (UPR), in GB pathophysiology. Special emphasis is placed on the UPR sensor IRE1, which regulates the secretory machinery in GB cells, influencing key processes such as protein maturation, trafficking, and cell migration. We propose that IRE1 may broadly affect protein secretion by directly influencing key molecular actors of the secretory pathway in GB cells. Specifically, we identified one IRE1 target, GOLIM4, a cis-Golgi protein involved in protein trafficking, whose silencing led to disrupted cell adhesion and enhanced migration, this suggests that IRE1 plays a crucial role in regulating protein transport and cell surface expression, which are vital for maintaining GB cell function and invasiveness.