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ST3GalIV drives SLeX biosynthesis in gastrointestinal cancer cells and associates with cancer cell motility
Expression of sialyl Lewis X (SLeX) is a well-documented event during malignant transformation of cancer cells, and largely associates with their invasive and metastatic properties. Glycoproteins and glycolipids are the main carriers of SLeX, whose biosynthesis is known to be performed by different...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10335957/ https://www.ncbi.nlm.nih.gov/pubmed/37074623 http://dx.doi.org/10.1007/s10719-023-10113-y |
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author | Costa, Ana F. Senra, Emanuel Faria-Ramos, Isabel Teixeira, Andreia Morais, João Pacheco, Mariana Reis, Celso A. Gomes, Catarina |
author_facet | Costa, Ana F. Senra, Emanuel Faria-Ramos, Isabel Teixeira, Andreia Morais, João Pacheco, Mariana Reis, Celso A. Gomes, Catarina |
author_sort | Costa, Ana F. |
collection | PubMed |
description | Expression of sialyl Lewis X (SLeX) is a well-documented event during malignant transformation of cancer cells, and largely associates with their invasive and metastatic properties. Glycoproteins and glycolipids are the main carriers of SLeX, whose biosynthesis is known to be performed by different glycosyltransferases, namely by the family of β-galactoside-α2,3-sialyltransferases (ST3Gals). In this study, we sought to elucidate the role of ST3GalIV in the biosynthesis of SLeX and in malignant properties of gastrointestinal (GI) cancer cells. By immunofluorescent screening, we selected SLeX-positive GI cancer cell lines and silenced ST3GalIV expression via CRISPR/Cas9. Flow cytometry, immunofluorescence and western blot analysis showed that ST3GalIV KO efficiently impaired SLeX expression in most cancer cell lines, with the exception of the colon cancer cell line LS174T. The impact of ST3GalIV KO in the biosynthesis of SLeX isomer SLeA and non sialylated Lewis X and A were also evaluated and overall, ST3GalIV KO led to a decreased expression of SLeA and an increased expression in both LeX and LeA. In addition, the abrogation of SLeX on GI cancer cells led to a reduction in cell motility. Furthermore, ST3GalVI KO was performed in LS174T ST3GalIV KO cells, resulting in the complete abolishment of SLeX expression and consequent reduced motility capacity of those cells. Overall, these findings portray ST3GalIV as the main, but not the only, enzyme driving the biosynthesis of SLeX in GI cancer cells, with a functional impact on cancer cell motility. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10719-023-10113-y. |
format | Online Article Text |
id | pubmed-10335957 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-103359572023-07-13 ST3GalIV drives SLeX biosynthesis in gastrointestinal cancer cells and associates with cancer cell motility Costa, Ana F. Senra, Emanuel Faria-Ramos, Isabel Teixeira, Andreia Morais, João Pacheco, Mariana Reis, Celso A. Gomes, Catarina Glycoconj J Research Expression of sialyl Lewis X (SLeX) is a well-documented event during malignant transformation of cancer cells, and largely associates with their invasive and metastatic properties. Glycoproteins and glycolipids are the main carriers of SLeX, whose biosynthesis is known to be performed by different glycosyltransferases, namely by the family of β-galactoside-α2,3-sialyltransferases (ST3Gals). In this study, we sought to elucidate the role of ST3GalIV in the biosynthesis of SLeX and in malignant properties of gastrointestinal (GI) cancer cells. By immunofluorescent screening, we selected SLeX-positive GI cancer cell lines and silenced ST3GalIV expression via CRISPR/Cas9. Flow cytometry, immunofluorescence and western blot analysis showed that ST3GalIV KO efficiently impaired SLeX expression in most cancer cell lines, with the exception of the colon cancer cell line LS174T. The impact of ST3GalIV KO in the biosynthesis of SLeX isomer SLeA and non sialylated Lewis X and A were also evaluated and overall, ST3GalIV KO led to a decreased expression of SLeA and an increased expression in both LeX and LeA. In addition, the abrogation of SLeX on GI cancer cells led to a reduction in cell motility. Furthermore, ST3GalVI KO was performed in LS174T ST3GalIV KO cells, resulting in the complete abolishment of SLeX expression and consequent reduced motility capacity of those cells. Overall, these findings portray ST3GalIV as the main, but not the only, enzyme driving the biosynthesis of SLeX in GI cancer cells, with a functional impact on cancer cell motility. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10719-023-10113-y. Springer US 2023-04-19 2023 /pmc/articles/PMC10335957/ /pubmed/37074623 http://dx.doi.org/10.1007/s10719-023-10113-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Costa, Ana F. Senra, Emanuel Faria-Ramos, Isabel Teixeira, Andreia Morais, João Pacheco, Mariana Reis, Celso A. Gomes, Catarina ST3GalIV drives SLeX biosynthesis in gastrointestinal cancer cells and associates with cancer cell motility |
title | ST3GalIV drives SLeX biosynthesis in gastrointestinal cancer cells and associates with cancer cell motility |
title_full | ST3GalIV drives SLeX biosynthesis in gastrointestinal cancer cells and associates with cancer cell motility |
title_fullStr | ST3GalIV drives SLeX biosynthesis in gastrointestinal cancer cells and associates with cancer cell motility |
title_full_unstemmed | ST3GalIV drives SLeX biosynthesis in gastrointestinal cancer cells and associates with cancer cell motility |
title_short | ST3GalIV drives SLeX biosynthesis in gastrointestinal cancer cells and associates with cancer cell motility |
title_sort | st3galiv drives slex biosynthesis in gastrointestinal cancer cells and associates with cancer cell motility |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10335957/ https://www.ncbi.nlm.nih.gov/pubmed/37074623 http://dx.doi.org/10.1007/s10719-023-10113-y |
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