Sarah-Maria Fendt (KU Leuven, Belgium), Metabolic rewiring driving metastasis formation
13 March 2023 | 8 h 00 min - 17 h 00 min
Sarah-Maria Fendt is since 2013 a Principal Investigator at the VIB Center for Cancer Biology and Professor of Oncology at KU Leuven, Belgium. Sarah’s lab is specifically interested in elucidating general regulatory principles in metabolism, and understanding cancer metabolism during metastasis formation as well as during altered whole body physiology. To perform novel research in her fields of interest her group exploits their expertise in metabolomics and fluxomics. The research of Sarah’s lab is currently funded by multiple (inter)national grants and industry, which include an ERC consolidator grant. Sarah received several awards such as the EMBO Gold Medal.
Research focus of Fendt’s lab: 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.