Investigation of Novel Roles for Pro-Survival protein Mcl-1 in Tumor Metabolism

• Applicant: Mohamed Elgendy, Ph.D.
• Subject Area: Cell Biology ; Hematology, Oncology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 491526833

Tumors rewire their metabolism to fuel rapid growth. Metabolic rewiring is linked to oncogenic switches. An important oncogenic switch is the upregulation of Mcl-1 (Elgendy et al., Nature Communications 2014). Mcl-1 inhibitors are in clinical testing. Tumor-promotion by Mcl-1 is typically attributed to its anti-apoptotic roles. However, we unraveled novel functions for Mcl-1 in autophagy and in response to metabolic crisis (Elgendy et al., Cancer Cell, 2019), suggesting a link with metabolism. Our preliminary data unravel novel role for Mcl-1 in the regulation of the central metabolic pathway mTORC1 and in bioenergetics through yet-to-unravel mechanisms. Analysis of patient samples further validated this link, which negatively correlated with survival. This proposal applies a system-approach utilizing advanced in vivo imaging, proteomic and metabolomic analyses to dissect the novel functions of Mcl-1 in the regulation of mTORC1 and bioenergetics and contribution to metastasis.The proposal offers realistic promise to deliver novel insights with immediate translational potential.

• DFG Programme: Research Grants
• International Connection: Czech Republic
• Cooperation Partner: Ludek Sefc, Ph.D.