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.

• Keywords
• EpCAM, colorectal carcinoma, desaturation, epithelial cells, fatty acid synthesis, lipidomics, lysophospholipids, phospholipids,
• MeSH
• Adenocarcinoma enzymology   genetics   metabolism   MeSH
• Fatty Acid Desaturases genetics   metabolism   MeSH
• Fatty Acid Elongases genetics   metabolism   MeSH
• Epithelial Cells enzymology   metabolism   MeSH
• Phospholipids metabolism   MeSH
• Humans MeSH
• Lipidomics MeSH
• Lipogenesis MeSH
• Fatty Acids metabolism   MeSH
• Lipid Metabolism * MeSH
• Colonic Neoplasms enzymology   genetics   metabolism   MeSH
• Gene Expression Regulation, Neoplastic * MeSH
• Aged MeSH
• Stearoyl-CoA Desaturase genetics   metabolism   MeSH
• Fatty Acid Synthases genetics   metabolism   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Fatty Acid Desaturases MeSH
• Fatty Acid Elongases MeSH
• ELOVL5 protein, human MeSH Browser
• FADS2 protein, human MeSH Browser
• Phospholipids MeSH
• Fatty Acids MeSH
• Stearoyl-CoA Desaturase MeSH
• Fatty Acid Synthases 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.

• Keywords
• colon cancer (CRC) sphingolipidomics, colon cancer cells, colorectal cancer, glycosphingolipid, lactosylceramide, sphingolipid, sphingosine-1-phosphate,
• MeSH
• Alkaline Ceramidase genetics   metabolism   MeSH
• Ceramides metabolism   MeSH
• Phosphotransferases (Alcohol Group Acceptor) genetics   metabolism   MeSH
• Acid Ceramidase genetics   metabolism   MeSH
• Lactosylceramides metabolism   MeSH
• Humans MeSH
• Lysophospholipids metabolism   MeSH
• Lipid Metabolism genetics   MeSH
• Disease Models, Animal MeSH
• Tumor Cells, Cultured MeSH
• Colonic Neoplasms enzymology   genetics   pathology   MeSH
• Neutral Ceramidase genetics   metabolism   MeSH
• Proto-Oncogene Proteins c-akt genetics   metabolism   MeSH
• Gene Expression Regulation, Neoplastic * MeSH
• Sphingolipids metabolism   MeSH
• Sphingosine N-Acyltransferase genetics   metabolism   MeSH
• Sphingosine analogs & derivatives   metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• ACER2 protein, human MeSH Browser
• Alkaline Ceramidase MeSH
• ASAH1 protein, human MeSH Browser
• ASAH2 protein, human MeSH Browser
• ceramide 1-phosphate MeSH Browser
• Ceramides MeSH
• Phosphotransferases (Alcohol Group Acceptor) MeSH
• Acid Ceramidase MeSH
• Lactosylceramides MeSH
• Lysophospholipids MeSH
• Neutral Ceramidase MeSH
• Proto-Oncogene Proteins c-akt MeSH
• Sphingolipids MeSH
• Sphingosine N-Acyltransferase MeSH
• Sphingosine MeSH
• sphingosine 1-phosphate MeSH Browser
• sphingosine kinase MeSH Browser