Division of Tumour Metabolism and Microenvironment
Prof. Dr. Almut Schulze
Tissue sections of tumours formed by p53-deficient human colon cancer cells showing induction of apoptosis upon depletion of the glycolytic regulator enzyme PFKFB4.
© dkfz.de
Metabolic reprogramming is an emerging hallmark of cancer. Altered metabolic activity in cancer cells drives the production of macromolecules for rapid proliferation and allows cancer cells to survive under conditions of nutrient and oxygen deprivation that is frequently found in tumours. Moreover, metabolic processes contribute to the heterotypic interactions between cancer cells and the surrounding stroma to facilitate cancer progression and immune evasion. The overall aim of our work is to unravel how oncogenic signalling pathways interact with the metabolic network to drive essential biosynthetic pathways that promote cancer cell expansion. We use RNAseq to monitor changes in metabolic gene expression and determine the transcriptional networks responsible for metabolic reprogramming in cancer. We also apply metabolomics using high-resolution LC/MS and metabolic flux analysis to determine alterations in metabolic activities of cancer cells. Moreover, we conduct targeted functional genetic screening to identify metabolic processes that are essential for the survival of cancer cells. A particular focus of our work are the sterol regulatory element binding proteins (SREBPs), a family of transcription factors that control the expression of enzymes involved in the synthesis of fatty acids and cholesterol. We are also interested in processes governing allosteric regulation of glycolysis and fatty acid synthesis and modification. We are currently investigating different molecular mechanisms controlling the expression and transcriptional activity of the SREBP transcription factors. We are also investigating the mechanisms by which SREBPs promote cancer cell survival and tumour growth. In particular, we are interested in the interactions between altered lipid metabolism and the regulation of cellular growth control and stress response in cancer cells. Another aspect of our research is the identification of selective metabolic vulnerabilities in cancer cells that could be targeted for cancer therapy. Here, we are particular interested in processes that allow cancer cells to adapt to the metabolic constraints of the tumour microenvironment, in particular tumour hypoxia and nutrient deprivation. Specific aspects of the tumour microenvironment can be modelled in vitro using specially formulated culture media and 3-dimensional culture systems. The role of specific metabolic processes during tumour development are investigated using genetic mouse models of cancer. We are also conducting in vivo screening to determine metabolic processes that are involved in cell transformation and metastasis formation. Furthermore, the metabolic interactions between cancer and immune cells will be a focus of our future work.
