脂肪酸去飽和異常促進乳腺癌形成
大多數腫瘤存在異常活化的脂質代謝，能夠促進脂肪酸的合成、延長、去飽和，幫助腫瘤細胞繁殖。不過，只有特定癌細胞亞型對靶向脂肪酸代謝尤其脂肪酸去飽和的方法敏感，表明許多癌細胞脂肪酸代謝具有未被闡明的癌症可塑性。
2019年2月6日，全球自然科學三大旗艦期刊之一、英國《自然》正刊在線發表比利時荷蘭語生物技術研究院、荷蘭語天主教魯汶大學、魯汶癌症研究院、布魯塞爾自由大學、法語天主教魯汶大學、日本福島大學、東京海洋大學、月島食品工業株式會社、英國牛津大學丘吉爾醫院、倫敦弗朗西斯·克里克研究院、德國拜耳、慕尼黑大學、德國癌症聯盟、海德堡大學、德國癌症研究中心、美國德克薩斯大學MD安德森癌症中心、德克薩斯大學西南醫學中心、紐約大學朗格醫學中心、霍華德休斯醫學研究院的研究報告，發現某些癌細胞可以利用脂肪酸去飽和替代途徑提高癌症可塑性，促進癌症形成。
該研究發現肝癌細胞（HUH7）、肺癌細胞（A549、H460）、前列癌細胞（DU145）、三陰性乳腺癌細胞（MDA-MB-468）、雌激素受體陽性乳腺癌細胞（T47D）可以將棕櫚酸酯（十六烷酸酯）去飽和為異常的十六碳烯酸酯，以幫助腫瘤細胞繁殖期間的細胞膜生物合成。十六碳烯酸酯生物合成使癌細胞能夠繞過依賴於硬脂醯（十八烷醯）輔酶A去飽和酶的已知脂肪酸去飽和途徑。
因此，只有針對兩種去飽和途徑，才能抑制癌細胞合成十六碳烯酸酯引起的體外和體內繁殖。該研究結果解釋了脂肪酸去飽和過程的代謝可塑性，並構成了未被闡明的癌症代謝異常途徑。
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
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