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 performed in 267 human breast tissues using ultra performance 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 to 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 based on 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, ELOVL1, FASN, INSIG1, SCAP, SCD, THRSP) 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.
- Received October 25, 2010.
- Revision received March 2, 2011.
- Accepted March 3, 2011.
- Copyright © 2011, American Association for Cancer Research.