Abstract
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.
Highlights
The development and progression of colorectal cancer (CRC), which is a major cause of cancer-related deaths in the western world, is accompanied with substantial changes of cellular lipidome, including alterations of fatty acid, phospholipid, and sphingolipid (SL) composition in tumor tissue
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
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
Summary
The development and progression of colorectal cancer (CRC), which is a major cause of cancer-related deaths in the western world, is accompanied with substantial changes of cellular lipidome, including alterations of fatty acid, phospholipid, and sphingolipid (SL) composition in tumor tissue. Levels of numerous lipid species have been found to be significantly altered in colon cancer tissue (as compared with normal colon mucosa) [1,2]. This has initiated an intensive search for the mechanisms responsible for these alterations, focusing primarily on the changes in expression/activities of lipid metabolism enzymes, as well as studies aiming to decipher the structural and signaling functions of the individually altered lipids [3,4]. We focus on the potential roles of SLs in colon cancer, as well as on potential benefits or setbacks of the currently used in vitro models of colon cancer cells in lipidomic studies focusing on SL metabolism. The changes in S1P/Cer ratio remain the best-characterized outcome of the alterations of SL metabolism in colon tumors [7]
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