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Complex Alterations of Fatty Acid Metabolism and Phospholipidome Uncovered in Isolated Colon Cancer Epithelial Cells

J. Hofmanová, J. Slavík, M. Ciganek, P. Ovesná, Z. Tylichová, M. Karasová, O. Zapletal, N. Straková, J. Procházková, J. Bouchal, Z. Kolář, J. Ehrmann, M. Levková, Z. Hušková, P. Skalický, A. Kozubík, M. Machala, J. Vondráček

. 2021 ; 22 (13) : . [pub] 20210622

Language English Country Switzerland

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc21025547

Grant support
15-30585A Ministerstvo Zdravotnictví Ceské Republiky
RVO: 68081707 Akademie Věd České Republiky
DRO-FNOL00098892 Ministerstvo Zdravotnictví Ceské Republiky
RO0520 Ministerstvo Zemědělství
CZ.02.1.01/0.0/0.0/15_003/0000495 Ministerstvo Školství, Mládeže a Tělovýchovy
CZ.02.1.01/0.0/0.0/16_019/0000868 Ministerstvo Školství, Mládeže a Tělovýchovy
CZ.02.1.01/0.0/0.0/16_013/0001674 Ministerstvo Školství, Mládeže a Tělovýchovy

The development of colon cancer, one of the most common malignancies, is accompanied with numerous lipid alterations. However, analyses of whole tumor samples may not always provide an accurate description of specific changes occurring directly in tumor epithelial cells. Here, we analyzed in detail the phospholipid (PL), lysophospholipid (lysoPL), and fatty acid (FA) profiles of purified EpCAM+ cells, isolated from tumor and adjacent non-tumor tissues of colon cancer patients. We found that a number of FAs increased significantly in isolated tumor cells, which also included a number of long polyunsaturated FAs. Higher levels of FAs were associated with increased expression of FA synthesis genes, as well as with altered expression of enzymes involved in FA elongation and desaturation, including particularly fatty acid synthase, stearoyl-CoA desaturase, fatty acid desaturase 2 and ELOVL5 fatty acid elongase 5 We identified significant changes in ratios of specific lysoPLs and corresponding PLs. A number of lysophosphatidylcholine and lysophosphatidylethanolamine species, containing long-chain and very-long chain FAs, often with high numbers of double bonds, were significantly upregulated in tumor cells. Increased de novo synthesis of very long-chain FAs, or, altered uptake or incorporation of these FAs into specific lysoPLs in tumor cells, may thus contribute to reprogramming of cellular phospholipidome and membrane alterations observed in colon cancer.

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