Characterizing the functions and relevance of 4EBP1 in glioblastoma

• Applicant: Dr. Gabriel Leprivier
• Subject Area: Molecular and Cellular Neurology and Neuropathology ; Cell Biology
• Term: from 2017 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 379877200

Glioblastoma (GBM) is an aggressive brain tumor, for which novel and more efficient therapeutic interventions are warranted. GBM are experiencing low nutrients conditions due to defects in the tumor vasculature. In consequence, GBM needs to develop molecular strategies to adapt to these stressful conditions. Understanding these strategies should reveal potential therapeutic targets for this disease. We identify 4EBP1, an mRNA translation regulator, as a potential cellular protective factor under nutrient deprivation. Strikingly, we observed that GBM patients exhibit high levels of 4EBP1 compared to healthy patients. Therefore, we propose to study the biological function and clinical relevance of 4EBP1 in GBM. To this aim, we will dissect at the molecular level how 4EBP1 may support GBM cells resistance to low nutrients conditions, including the impact on metabolism. In addition, the function of 4EBP1 in supporting GBM progression will be assessed in vivo using mouse models. Finally, we will characterize the relevance of 4EBP1 for prognosis of GBM patients using a large collection of GBM samples available to us. Overall, the goal of our proposed project is to explore the biological role of 4EBP1 in GBM and its relevance for patients prognosis, with the potential of determining whether 4EBP1 may be a therapeutic target in this disease.

• DFG Programme: Research Grants