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Transition of Mesenchymal and Epithelial Cancer Cells Depends on α1-4 Galactosyltransferase-Mediated Glycosphingolipids

Jacob, Francis and Alam, Shahidul and Konantz, Martina and Liang, Ching-Yeu and Kohler, Reto S. and Everest-Dass, Arun V. and Huang, Yen-Lin and Rimmer, Natalie and Fedier, Andre and Schötzau, Andreas and Lopez, Monica Nunez and Packer, Nicolle H. and Lengerke, Claudia and Heinzelmann-Schwarz, Viola. (2018) Transition of Mesenchymal and Epithelial Cancer Cells Depends on α1-4 Galactosyltransferase-Mediated Glycosphingolipids. Cancer Research, 78 (11). pp. 2952-2965.

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Official URL: https://edoc.unibas.ch/80790/

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Abstract

The reversible transitions of cancer cells between epithelial and mesenchymal states comprise cellular and molecular processes essential for local tumor growth and respective dissemination. We report here that globoside glycosphingolipid (GSL) glycosyltransferase-encoding genes are elevated in epithelial cells and correlate with characteristic EMT signatures predictive of disease outcome. Depletion of globosides through CRISPR-Cas9–mediated deletion of the key enzyme A4GALT induces EMT, enhances chemoresistance, and increased CD24low/CD44high cells. The cholera toxin–induced mesenchymal-to-epithelial transition occurred only in cells with functional A4GALT. Cells undergoing EMT lost E-cadherin expression through epigenetic silencing at the promoter region of CDH1. However, in ΔA4GALT cells, demethylation was able to rescue E-cadherin–mediated cell–cell adhesion only in the presence of exogenous A4GALT. Overall, our data suggest another class of biomolecules vital for epithelial cancer cells and for maintaining cell integrity and function.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin
UniBasel Contributors:Konantz, Martina
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Association for Cancer Research
ISSN:0008-5472
e-ISSN:1538-7445
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:09 Jun 2021 13:45
Deposited On:09 Jun 2021 13:45

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