Vriens, Kim Christen, Stefan Parik, Sweta Broekaert, Dorien Yoshinaga, Kazuaki Talebi, Ali Dehairs, Jonas Escalona-Noguero, Carmen Schmieder, Roberta Cornfield, Thomas Charlton, Catriona Romero-Pérez, Laura Rossi, Matteo Rinaldi, Gianmarco Orth, Martin F Boon, Ruben Kerstens, Axelle Kwan, Suet Ying Faubert, Brandon Méndez-Lucas, Andrés Kopitz, Charlotte C Chen, Ting Fernandez-Garcia, Juan Duarte, João AG Schmitz, Arndt A Steigemann, Patrick Najimi, Mustapha Hägebarth, Andrea Van Ginderachter, Jo A Sokal, Etienne Gotoh, Naohiro Wong, Kwok-Kin Verfaillie, Catherine Derua, Rita Munck, Sebastian Yuneva, Mariia Beretta, Laura DeBerardinis, Ralph J Swinnen, Johannes V Hodson, Leanne Cassiman, David Verslype, Chris Christian, Sven Grünewald, Sylvia Grünewald, Thomas GP Fendt, Sarah-Maria Evidence for an alternative fatty acid desaturation pathway increasing cancer plasticity Most tumours have an aberrantly activated lipid metabolism1,2 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 desaturation3. This suggests that many cancer cells contain an unexplored plasticity in their fatty acid metabolism. Here we show 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. Animals;Cell Line, Tumor;Cell Membrane;Cell Proliferation;Fatty Acid Desaturases;Fatty Acids;Female;HEK293 Cells;Humans;Male;Metabolic Networks and Pathways;Mice;Neoplasms;Oleic Acids;Palmitates;Palmitic Acids;Stearoyl-CoA Desaturase;Yuneva FC001223;General Science & Technology 2019-12-19
    https://crick.figshare.com/articles/journal_contribution/Evidence_for_an_alternative_fatty_acid_desaturation_pathway_increasing_cancer_plasticity/11410008