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Knock-out of 5-lipoxygenase in overexpressing tumor cells—consequences on gene expression and cellular function
5-Lipoxygenase (5-LO), the central enzyme in the biosynthesis of leukotrienes, is frequently expressed in human solid malignancies even though the enzyme is not present in the corresponding healthy tissues. There is little knowledge on the consequences of this expression for the tumor cells regardin...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group US
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9842508/ https://www.ncbi.nlm.nih.gov/pubmed/36114329 http://dx.doi.org/10.1038/s41417-022-00531-9 |
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author | Weisser, Hannah Göbel, Tamara Melissa Krishnathas, G. Kreiß, Marius Angioni, Carlo Sürün, Duran Thomas, Dominique Schmid, Tobias Häfner, Ann-Kathrin Kahnt, Astrid S. |
author_facet | Weisser, Hannah Göbel, Tamara Melissa Krishnathas, G. Kreiß, Marius Angioni, Carlo Sürün, Duran Thomas, Dominique Schmid, Tobias Häfner, Ann-Kathrin Kahnt, Astrid S. |
author_sort | Weisser, Hannah |
collection | PubMed |
description | 5-Lipoxygenase (5-LO), the central enzyme in the biosynthesis of leukotrienes, is frequently expressed in human solid malignancies even though the enzyme is not present in the corresponding healthy tissues. There is little knowledge on the consequences of this expression for the tumor cells regarding gene expression and cellular function. We established a knockout (KO) of 5-LO in different cancer cell lines (HCT-116, HT-29, U-2 OS) and studied the consequences on global gene expression using next generation sequencing. Furthermore, cell viability, proliferation, migration and multicellular tumor spheroid (MCTS) formation were studied in these cells. Our results show that 5-LO influences the gene expression and cancer cell function in a cell type-dependent manner. The enzyme affected genes involved in cell adhesion, extracellular matrix formation, G protein signaling and cytoskeleton organization. Furthermore, absence of 5-LO elevated TGFβ(2) expression in HCT-116 cells while MCP-1, fractalkine and platelet-derived growth factor expression was attenuated in U-2 OS cells suggesting that tumor cell-derived 5-LO shapes the tumor microenvironment. In line with the gene expression data, KO of 5-LO had an impact on cell proliferation, motility and MCTS formation. Interestingly, pharmacological inhibition of 5-LO only partly mimicked the KO suggesting that also noncanonical functions are involved. |
format | Online Article Text |
id | pubmed-9842508 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group US |
record_format | MEDLINE/PubMed |
spelling | pubmed-98425082023-01-18 Knock-out of 5-lipoxygenase in overexpressing tumor cells—consequences on gene expression and cellular function Weisser, Hannah Göbel, Tamara Melissa Krishnathas, G. Kreiß, Marius Angioni, Carlo Sürün, Duran Thomas, Dominique Schmid, Tobias Häfner, Ann-Kathrin Kahnt, Astrid S. Cancer Gene Ther Article 5-Lipoxygenase (5-LO), the central enzyme in the biosynthesis of leukotrienes, is frequently expressed in human solid malignancies even though the enzyme is not present in the corresponding healthy tissues. There is little knowledge on the consequences of this expression for the tumor cells regarding gene expression and cellular function. We established a knockout (KO) of 5-LO in different cancer cell lines (HCT-116, HT-29, U-2 OS) and studied the consequences on global gene expression using next generation sequencing. Furthermore, cell viability, proliferation, migration and multicellular tumor spheroid (MCTS) formation were studied in these cells. Our results show that 5-LO influences the gene expression and cancer cell function in a cell type-dependent manner. The enzyme affected genes involved in cell adhesion, extracellular matrix formation, G protein signaling and cytoskeleton organization. Furthermore, absence of 5-LO elevated TGFβ(2) expression in HCT-116 cells while MCP-1, fractalkine and platelet-derived growth factor expression was attenuated in U-2 OS cells suggesting that tumor cell-derived 5-LO shapes the tumor microenvironment. In line with the gene expression data, KO of 5-LO had an impact on cell proliferation, motility and MCTS formation. Interestingly, pharmacological inhibition of 5-LO only partly mimicked the KO suggesting that also noncanonical functions are involved. Nature Publishing Group US 2022-09-16 2023 /pmc/articles/PMC9842508/ /pubmed/36114329 http://dx.doi.org/10.1038/s41417-022-00531-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Weisser, Hannah Göbel, Tamara Melissa Krishnathas, G. Kreiß, Marius Angioni, Carlo Sürün, Duran Thomas, Dominique Schmid, Tobias Häfner, Ann-Kathrin Kahnt, Astrid S. Knock-out of 5-lipoxygenase in overexpressing tumor cells—consequences on gene expression and cellular function |
title | Knock-out of 5-lipoxygenase in overexpressing tumor cells—consequences on gene expression and cellular function |
title_full | Knock-out of 5-lipoxygenase in overexpressing tumor cells—consequences on gene expression and cellular function |
title_fullStr | Knock-out of 5-lipoxygenase in overexpressing tumor cells—consequences on gene expression and cellular function |
title_full_unstemmed | Knock-out of 5-lipoxygenase in overexpressing tumor cells—consequences on gene expression and cellular function |
title_short | Knock-out of 5-lipoxygenase in overexpressing tumor cells—consequences on gene expression and cellular function |
title_sort | knock-out of 5-lipoxygenase in overexpressing tumor cells—consequences on gene expression and cellular function |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9842508/ https://www.ncbi.nlm.nih.gov/pubmed/36114329 http://dx.doi.org/10.1038/s41417-022-00531-9 |
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