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Colon Cancer and Perturbations of the Sphingolipid Metabolism

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...

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Autores principales: Machala, Miroslav, Procházková, Jiřina, Hofmanová, Jiřina, Králiková, Lucie, Slavík, Josef, Tylichová, Zuzana, Ovesná, Petra, Kozubík, Alois, Vondráček, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929044/
https://www.ncbi.nlm.nih.gov/pubmed/31801289
http://dx.doi.org/10.3390/ijms20236051
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author Machala, Miroslav
Procházková, Jiřina
Hofmanová, Jiřina
Králiková, Lucie
Slavík, Josef
Tylichová, Zuzana
Ovesná, Petra
Kozubík, Alois
Vondráček, Jan
author_facet Machala, Miroslav
Procházková, Jiřina
Hofmanová, Jiřina
Králiková, Lucie
Slavík, Josef
Tylichová, Zuzana
Ovesná, Petra
Kozubík, Alois
Vondráček, Jan
author_sort Machala, Miroslav
collection PubMed
description 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.
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spelling pubmed-69290442019-12-26 Colon Cancer and Perturbations of the Sphingolipid Metabolism Machala, Miroslav Procházková, Jiřina Hofmanová, Jiřina Králiková, Lucie Slavík, Josef Tylichová, Zuzana Ovesná, Petra Kozubík, Alois Vondráček, Jan Int J Mol Sci Review 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. MDPI 2019-11-30 /pmc/articles/PMC6929044/ /pubmed/31801289 http://dx.doi.org/10.3390/ijms20236051 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Machala, Miroslav
Procházková, Jiřina
Hofmanová, Jiřina
Králiková, Lucie
Slavík, Josef
Tylichová, Zuzana
Ovesná, Petra
Kozubík, Alois
Vondráček, Jan
Colon Cancer and Perturbations of the Sphingolipid Metabolism
title Colon Cancer and Perturbations of the Sphingolipid Metabolism
title_full Colon Cancer and Perturbations of the Sphingolipid Metabolism
title_fullStr Colon Cancer and Perturbations of the Sphingolipid Metabolism
title_full_unstemmed Colon Cancer and Perturbations of the Sphingolipid Metabolism
title_short Colon Cancer and Perturbations of the Sphingolipid Metabolism
title_sort colon cancer and perturbations of the sphingolipid metabolism
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929044/
https://www.ncbi.nlm.nih.gov/pubmed/31801289
http://dx.doi.org/10.3390/ijms20236051
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