Activation of lipid metabolism is an early event in carcinogenesis and a central hallmark of many cancers. However, the precise molecular composition of lipids in tumors remains generally poorly characterized. The aim of the present study was to analyze the global lipid profiles of breast cancer, integrate the results to protein expression, and validate the findings by functional experiments. Comprehensive lipidomics was conducted in 267 human breast tissues using ultraperformance liquid chromatography/ mass spectrometry. The products of de novo fatty acid synthesis incorporated into membrane phospholipids, such as palmitate-containing phosphatidylcholines, were increased in tumors as compared with normal breast tissues. These lipids were associated with cancer progression and patient survival, as their concentration was highest in estrogen receptor–negative and grade 3 tumors. In silico transcriptomics database was utilized in investigating the expression of lipid metabolism related genes in breast cancer, and on the basis of these results, the expression of specific proteins was studied by immunohistochemistry. Immunohistochemical analyses showed that several genes regulating lipid metabolism were highly expressed in clinical breast cancer samples and supported also the lipidomics results. Gene silencing experiments with seven genes [ACACA (acetyl-CoA carboxylase α), ELOVL1 (elongation of very long chain fatty acid–like 1), FASN (fatty acid synthase), INSIG1 (insulin-induced gene 1), SCAP (sterol regulatory element–binding protein cleavage–activating protein), SCD (stearoyl-CoA desaturase), and THRSP (thyroid hormone–responsive protein)] indicated that silencing of multiple lipid metabolism–regulating genes reduced the lipidomic profiles and viability of the breast cancer cells. Taken together, our results imply that phospholipids may have diagnostic potential as well as that modulation of their metabolism may provide therapeutic opportunities in breast cancer treatment. Cancer Res; 71(9); 3236–45. ©2011 AACR.

John A. Bowden, Alan Heckert, Candice Z. Ulmer, Christina M. Jones, Jeremy P. Koelmel, Laila Abdullah, Linda Ahonen, Yazen Alnouti, Aaron M. Armando, John M. Asara, Takeshi Bamba, John R. Barr, Jonas Bergquist, Christoph H. Borchers, Joost Brandsma, Susanne B. Breitkopf, Tomas Cajka, Amaury Cazenave-Gassiot, Antonio Checa, Michelle A. Cinel, Romain A. Colas, Serge Cremers, Edward A. Dennis, James E. Evans, Alexander Fauland, Oliver Fiehn, Michael S. Gardner, Timothy J. Garrett, Katherine H. Gotlinger, Jun Han, Yingying Huang, Aveline Huipeng Neo, Tuulia Hyötyläinen, Yoshihiro Izumi, Hongfeng Jiang, Houli Jiang, Jiang Jiang, Maureen Kachman, Reiko Kiyonami, Kristaps Klavins, Christian Klose, Harald C. Köfeler, Johan Kolmert, Therese Koal, Grielof Koster, Zsuzsanna Kuklenyik, Irwin J. Kurland, Michael Leadley, Karen Lin, Krishna Rao Maddipati, Danielle McDougall, Peter J. Meikle, Natalie A. Mellett, Cian Monnin, M. Arthur Moseley, Renu Nandakumar, Matej Oresic, Rainey Patterson, David Peake, Jason S. Pierce, Martin Post, Anthony D. Postle, Rebecca Pugh, Yunping Qiu, Oswald Quehenberger, Parsram Ramrup, Jon Rees, Barbara Rembiesa, Denis Reynaud, Mary R. Roth, Susanne Sales, Kai Schuhmann, Michal Laniado Schwartzman, Charles N. Serhan, Andrej Shevchenko, Stephen E. Somerville, Lisa St. John-Williams, Michal A. Surma, Hiroaki Takeda, Rhishikesh Thakare, J. Will Thompson, Federico Torta, Alexander Triebl, Martin Trötzmüller, S. J. Kumari Ubhayasekera, Dajana Vuckovic, Jacquelyn M. Weir, Ruth Welti, Markus R. Wenk, Craig E. Wheelock, Libin Yao, Min Yuan, Xueqing Heather Zhao, Senlin Zhou