PUBLICATION
Transition of Mesenchymal and Epithelial Cancer Cells Depends on α1-4 Galactosyltransferase-Mediated Glycosphingolipids
- Authors
- Jacob, F., Alam, S., Konantz, M., Liang, C.Y., Kohler, R.S., Everest-Dass, A.V., Huang, Y.L., Rimmer, N., Fedier, A., Schötzau, A., Lopez, M.N., Packer, N.H., Lengerke, C., Heinzelmann-Schwarz, V.
- ID
- ZDB-PUB-190614-24
- Date
- 2018
- Source
- Cancer research 78: 2952-2965 (Journal)
- Registered Authors
- Konantz, Martina, Lengerke, Claudia
- Keywords
- none
- MeSH Terms
-
- Zebrafish
- Promoter Regions, Genetic/genetics
- CRISPR-Cas Systems/genetics
- Animals
- Galactosyltransferases/genetics*
- Gene Expression Regulation, Neoplastic/genetics
- Gene Expression Profiling/methods
- Epithelial-Mesenchymal Transition/genetics*
- CD24 Antigen/genetics
- Humans
- Hyaluronan Receptors/genetics
- Cell Line, Tumor
- Globosides/metabolism*
- Epigenesis, Genetic/genetics
- Cell Adhesion/genetics
- Cadherins/genetics
- Glycosphingolipids/genetics*
- Epithelial Cells/pathology
- PubMed
- 29572228 Full text @ Cancer Res.
Citation
Jacob, F., Alam, S., Konantz, M., Liang, C.Y., Kohler, R.S., Everest-Dass, A.V., Huang, Y.L., Rimmer, N., Fedier, A., Schötzau, A., Lopez, M.N., Packer, N.H., Lengerke, C., Heinzelmann-Schwarz, V. (2018) Transition of Mesenchymal and Epithelial Cancer Cells Depends on α1-4 Galactosyltransferase-Mediated Glycosphingolipids. Cancer research. 78:2952-2965.
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.Significance: This study highlights the essential role of glycosphingolipids in the maintenance of epithelial cancer cell properties. Cancer Res; 78(11); 2952-65. ©2018 AACR.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping