Glioblastoma Survival Signaling Lab
Our laboratory aims to understand how cancer signaling molecules and pathways regulate the pro-tumorigenic characteristics of glioblastoma, the most aggressive and lethal brain tumour in adults. Along with being highly proliferative and invasive, glioblastoma cells are also capable of surviving in sub-optimal conditions such as nutrient and oxygen-poor environments. However, the exact signaling pathways used by glioblastoma cells to tolerate and survive these sub-optimal conditions are not completely known. Recently, our lab has begun to elucidate the signaling pathways that promote cell survival when cells are in low nutrient or oxygen conditions. Specifically, we have identified a novel growth factor and cytokine-dependent mechanism that promotes glioblastoma survival. Using primary patient-derived glioblastoma cells; we have uncovered a novel signaling network involving the activation of the glutamine metabolic pathway under glucose-starved conditions. This glutamine metabolic pathway protects glioblastoma cells from cell death by inhibiting endoplasmic reticulum stress mediated apoptosis thereby providing glioblastoma cells with a survival advantage over cells that do not utilise this novel signaling cascade.
Importantly, these discoveries provide rationale for targeting the glutamine metabolic pathway as a therapeutic approach in glioblastoma. Our current research will expand on these findings with our over-arching hypothesis that glioblastoma cells drive enhanced glutamine metabolism leading to reduced ER stress, reduced ER-mitochondrial interaction, reduced mitochondrial Ca2+ uptake and increased glioblastoma cell survival.
View Dr Rod Luwor's latest PubMed publications here
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