mTOR-mediated deregulation of mitochondrial metabolism in hepatocellular carcinoma (HCC)

• Applicant: Dr. Dirk Mossmann
• Subject Area: Cell Biology ; Biochemistry
• Term: from 2016 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 324225723

Cancer is the leading cause of death worldwide, and the development of therapy resistance and tumor relapse prevents eradication of the disease. Extensive research has revealed that cancer is due to deregulated signaling pathways as well as metabolic alterations. Therefore, specific therapies targeting these cancer-mediating signaling pathways have been developed. However, cancer cells develop therapy resistance by activating compensatory signaling pathways and metabolic reprogramming. The serine/threonine kinase mammalian target of rapamycin (mTOR), the central controller of cellular growth and metabolism, is frequently activated in many types of cancer. Mitochondria are key players in cellular metabolism and are implicated in several of the processes known as the hallmarks of cancer.Little is known so far about the connection between mTOR, mitochondria and the alterations in cellular metabolism in the context of cancer development and therapy resistance. I propose to investigate how deregulation of mTOR in hepatocellular carcinoma (HCC) alters mitochondrial metabolism leading to tumor progression and therapy resistance. Available unpublished proteomic data from both HCC patients and an HCC mouse model with upregulated mTOR signaling will allow identification, validation and in-depth analysis of mitochondrial alterations that might be causal for HCC. Insights gained will i) explain how deregulated mTOR signaling alters mitochondrial metabolism, ii) reveal molecular pathomechanisms in oncogenesis, and iii) identify potential novel drug targets and biomarkers for HCC.

• DFG Programme: Research Fellowships
• International Connection: Switzerland
• Host: Professor Dr. Michael N. Hall