P2 - AG Fandrey Tina Schönberger

 Role of hypoxia on lipid signaling

The transcription factor hypoxia inducible factor-1 (HIF-1) controls and mediates the gene expression within hypoxic tumor tissue and plays therefor an important role in cancer treatment. Tumor angiogenesis, adaption of tumor metabolism to low nutrient and oxygen levels, genetic instability and metastasis in tumor cells are controlled by activated HIF-1. Furthermore, sphingolipids are known to be oxygen-independent regulators of HIFs and are important cell mediators in tumor and inflammatory hypoxia. We will study the connection between hypoxia and HIF activation on lipid signaling by studying mouse embryonic fibroblasts (MEFs) and bone marrow derived macrophages (BMDMs) derived from mice with altered sphingolipid levels. Thereby we will focus on the importance of the acid sphingomyelinase (Asm), acid ceramidase (AC) and sphingosine 1-phosphate (S1P) pathway. As recent findings of our group indicate a change in the HIF response mechanisms in case of altered sphingosine-1-phosphate levels, we further aim to investigate functional differences in the mechanisms of HIF accumulation under normoxic and hypoxic conditions.