脂肪酸去饱和异常促进乳腺癌形成
大多数肿瘤存在异常活化的脂质代谢，能够促进脂肪酸的合成、延长、去饱和，帮助肿瘤细胞繁殖。不过，只有特定癌细胞亚型对靶向脂肪酸代谢尤其脂肪酸去饱和的方法敏感，表明许多癌细胞脂肪酸代谢具有未被阐明的癌症可塑性。
2019年2月6日，全球自然科学三大旗舰期刊之一、英国《自然》正刊在线发表比利时荷兰语生物技术研究院、荷兰语天主教鲁汶大学、鲁汶癌症研究院、布鲁塞尔自由大学、法语天主教鲁汶大学、日本福岛大学、东京海洋大学、月岛食品工业株式会社、英国牛津大学丘吉尔医院、伦敦弗朗西斯·克里克研究院、德国拜耳、慕尼黑大学、德国癌症联盟、海德堡大学、德国癌症研究中心、美国德克萨斯大学MD安德森癌症中心、德克萨斯大学西南医学中心、纽约大学朗格医学中心、霍华德休斯医学研究院的研究报告，发现某些癌细胞可以利用脂肪酸去饱和替代途径提高癌症可塑性，促进癌症形成。
该研究发现肝癌细胞（HUH7）、肺癌细胞（A549、H460）、前列癌细胞（DU145）、三阴性乳腺癌细胞（MDA-MB-468）、雌激素受体阳性乳腺癌细胞（T47D）可以将棕榈酸酯（十六烷酸酯）去饱和为异常的十六碳烯酸酯，以帮助肿瘤细胞繁殖期间的细胞膜生物合成。十六碳烯酸酯生物合成使癌细胞能够绕过依赖于硬脂酰（十八烷酰）辅酶A去饱和酶的已知脂肪酸去饱和途径。
因此，只有针对两种去饱和途径，才能抑制癌细胞合成十六碳烯酸酯引起的体外和体内繁殖。该研究结果解释了脂肪酸去饱和过程的代谢可塑性，并构成了未被阐明的癌症代谢异常途径。
Nature. 2019 Feb 6. [Epub ahead of print]
Evidence for an alternative fatty acid desaturation pathway increasing cancer plasticity.
Kim Vriens, Stefan Christen, Sweta Parik, Dorien Broekaert, Kazuaki Yoshinaga, Ali Talebi, Jonas Dehairs, Carmen Escalona-Noguero, Roberta Schmieder, Thomas Cornfield, Catriona Charlton, Laura Romero-Pérez, Matteo Rossi, Gianmarco Rinaldi, Martin F. Orth, Ruben Boon, Axelle Kerstens, Suet Ying Kwan, Brandon Faubert, Andrés Méndez-Lucas, Charlotte C. Kopitz, Ting Chen, Juan Fernandez-Garcia, Joao A. G. Duarte, Arndt A. Schmitz, Patrick Steigemann, Mustapha Najimi, Andrea Hagebarth, Jo A. Van Ginderachter, Etienne Sokal, Naohiro Gotoh, Kwok-Kin Wong, Catherine Verfaillie, Rita Derua, Sebastian Munck, Mariia Yuneva, Laura Beretta, Ralph J. DeBerardinis, Johannes V. Swinnen, Leanne Hodson, David Cassiman, Chris Verslype, Sven Christian, Sylvia Grünewald, Thomas G. P. Grünewald, Sarah-Maria Fendt.
VIB, Leuven, Belgium; KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium; Vrije Universiteit Brussel, Brussels, Belgium; VIB Center for Inflammation Research, Brussels, Belgium; Tsukishima Foods Industry, Tokyo, Japan; Fukushima University, Fukushima, Japan; Leuven Cancer Institute (LKI), Leuven, Belgium; University of Oxford, Churchill Hospital, Oxford, UK; LMU Munich, Munich, Germany; KU Leuven, Leuven, Belgium; University of Texas MD Anderson Cancer Center, Houston, TX, USA; UT Southwestern, Dallas, TX, USA; The Francis Crick Institute, London, UK; Bayer AG, Research & Development, Pharmaceuticals, Berlin, Germany; Perlmutter Cancer Center, NYU Langone Medical Center, Smilow Research Center, New York, NY, USA; Université Catholique de Louvain and Cliniques Universitaires St Luc, Brussels, Belgium; Tokyo University of Marine Science and Technology, Tokyo, Japan; Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, TX, USA; German Cancer Consortium (DKTK), Partner site Munich, Munich, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany.
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 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.
DOI: 10.1038/s41586-019-0904-1
（此文为转载）