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.

• MeSH
• adenokarcinom enzymologie   genetika   metabolismus   MeSH
• desaturasy mastných kyselin genetika   metabolismus   MeSH
• elongasy mastných kyselin genetika   metabolismus   MeSH
• epitelové buňky enzymologie   metabolismus   MeSH
• fosfolipidy metabolismus   MeSH
• lidé MeSH
• lipidomika MeSH
• lipogeneze MeSH
• mastné kyseliny metabolismus   MeSH
• metabolismus lipidů * MeSH
• nádory tračníku enzymologie   genetika   metabolismus   MeSH
• regulace genové exprese u nádorů * MeSH
• senioři MeSH
• stearyl-CoA-desaturasa genetika   metabolismus   MeSH
• syntázy mastných kyselin genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The development and progression of colorectal cancer (CRC), a major cause of cancer-related death in the western world, is accompanied with alterations of sphingolipid (SL) composition in colon tumors. A number of enzymes involved in the SL metabolism have been found to be deregulated in human colon tumors, in experimental rodent studies, and in human colon cancer cells in vitro. Therefore, the enzymatic pathways that modulate SL levels have received a significant attention, due to their possible contribution to CRC development, or as potential therapeutic targets. Many of these enzymes are associated with an increased sphingosine-1-phosphate/ceramide ratio, which is in turn linked with increased colon cancer cell survival, proliferation and cancer progression. Nevertheless, more attention should also be paid to the more complex SLs, including specific glycosphingolipids, such as lactosylceramides, which can be also deregulated during CRC development. In this review, we focus on the potential roles of individual SLs/SL metabolism enzymes in colon cancer, as well as on the pros and cons of employing the current in vitro models of colon cancer cells for lipidomic studies investigating the SL metabolism in CRC.

• MeSH
• alkalická ceramidasa genetika   metabolismus   MeSH
• ceramidy metabolismus   MeSH
• fosfotransferasy s alkoholovou skupinou jako akceptorem genetika   metabolismus   MeSH
• kyselá ceramidasa genetika   metabolismus   MeSH
• laktosylceramidy metabolismus   MeSH
• lidé MeSH
• lysofosfolipidy metabolismus   MeSH
• metabolismus lipidů genetika   MeSH
• modely nemocí na zvířatech MeSH
• nádorové buňky kultivované MeSH
• nádory tračníku enzymologie   genetika   patologie   MeSH
• neutrální ceramidasa genetika   metabolismus   MeSH
• protoonkogenní proteiny c-akt genetika   metabolismus   MeSH
• regulace genové exprese u nádorů * MeSH
• sfingolipidy metabolismus   MeSH
• sfingosin-N-acyltransferasa genetika   metabolismus   MeSH
• sfingosin analogy a deriváty   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH