Laboratory of Cellular Metabolism and Metabolic Regulation
We are tackling cancer and in particular metastasis formation as a metabolic disease. The rationale for this innovative approach is based on the fact that cancer and specifically metastasizing cells have to dynamically alter their cellular phenotype during disease progression, which in turn requires metabolic changes. Therefore, the overarching vision of my laboratory is to mechanistically dissect the metabolic vulnerabilities of (metastasizing) cancer cells in the context of the tumor microenvironment and the metastatic niche to define novel therapeutic approaches to prevent cancer progression.
Do cancer cells have placticity in their lipid metabolism?
Most tumours have an aberrantly activated lipid metabolism that enables them to synthesize, elongate and desaturate fatty acids to support proliferation. However, only particular subsets of cancer cells are sensitive to approaches that target fatty acid metabolism and, in particular, fatty acid desaturation. This suggests that many cancer cells contain an unexplored plasticity in their fatty acid metabolism. Here we discovered that some cancer cells can exploit an alternative fatty acid desaturation pathway. We identify various cancer cell lines, mouse hepatocellular carcinomas, and primary human liver and lung carcinomas that desaturate palmitate to the unusual fatty acid sapienate to support membrane biosynthesis during proliferation. Accordingly, we found that sapienate biosynthesis enables cancer cells to bypass the known fatty acid desaturation pathway that is dependent on stearoyl-CoA desaturase. Thus, only by targeting both desaturation pathways is the in vitro and in vivo proliferation of cancer cells that synthesize sapienate impaired. Our discovery explains metabolic plasticity in fatty acid desaturation and constitutes an unexplored metabolic rewiring in cancers.
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