Role of glycosylation in TGF-β signaling and epithelial-to-mesenchymal transition in cancer
Abstract Glycosylation is a common posttranslational modification on membrane-associated and secreted proteins that is of pivotal importance for regulating cell functions. Aberrant glycosylation can lead to uncontrolled cell proliferation, cell-matrix interactions, migration and differentiation, and...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Oxford University Press
2020-06-01
|
| Series: | Protein & Cell |
| Subjects: | |
| Online Access: | https://doi.org/10.1007/s13238-020-00741-7 |
| _version_ | 1797716060911173632 |
|---|---|
| author | Jing Zhang Peter ten Dijke Manfred Wuhrer Tao Zhang |
| author_facet | Jing Zhang Peter ten Dijke Manfred Wuhrer Tao Zhang |
| author_sort | Jing Zhang |
| collection | DOAJ |
| description | Abstract Glycosylation is a common posttranslational modification on membrane-associated and secreted proteins that is of pivotal importance for regulating cell functions. Aberrant glycosylation can lead to uncontrolled cell proliferation, cell-matrix interactions, migration and differentiation, and has been shown to be involved in cancer and other diseases. The epithelial-to-mesenchymal transition is a key step in the metastatic process by which cancer cells gain the ability to invade tissues and extravasate into the bloodstream. This cellular transformation process, which is associated by morphological change, loss of epithelial traits and gain of mesenchymal markers, is triggered by the secreted cytokine transforming growth factor-β (TGF-β). TGF-β bioactivity is carefully regulated, and its effects on cells are mediated by its receptors on the cell surface. In this review, we first provide a brief overview of major types of glycans, namely, N-glycans, O-glycans, glycosphingolipids and glycosaminoglycans that are involved in cancer progression. Thereafter, we summarize studies on how the glycosylation of TGF-β signaling components regulates TGF-β secretion, bioavailability and TGF-β receptor function. Then, we review glycosylation changes associated with TGF-β-induced epithelial-to-mesenchymal transition in cancer. Identifying and understanding the mechanisms by which glycosylation affects TGF-β signaling and downstream biological responses will facilitate the identification of glycans as biomarkers and enable novel therapeutic approaches. |
| first_indexed | 2024-03-12T08:15:56Z |
| format | Article |
| id | doaj.art-8e082e0f4b114d3998b03f45ca10035e |
| institution | Directory Open Access Journal |
| issn | 1674-800X 1674-8018 |
| language | English |
| last_indexed | 2024-03-12T08:15:56Z |
| publishDate | 2020-06-01 |
| publisher | Oxford University Press |
| record_format | Article |
| series | Protein & Cell |
| spelling | doaj.art-8e082e0f4b114d3998b03f45ca10035e2023-09-02T18:55:16ZengOxford University PressProtein & Cell1674-800X1674-80182020-06-011228910610.1007/s13238-020-00741-7Role of glycosylation in TGF-β signaling and epithelial-to-mesenchymal transition in cancerJing Zhang0Peter ten Dijke1Manfred Wuhrer2Tao Zhang3Oncode Institute and Cell Chemical Biology, Leiden University Medical CenterOncode Institute and Cell Chemical Biology, Leiden University Medical CenterCenter for Proteomics and Metabolomics, Leiden University Medical CenterCenter for Proteomics and Metabolomics, Leiden University Medical CenterAbstract Glycosylation is a common posttranslational modification on membrane-associated and secreted proteins that is of pivotal importance for regulating cell functions. Aberrant glycosylation can lead to uncontrolled cell proliferation, cell-matrix interactions, migration and differentiation, and has been shown to be involved in cancer and other diseases. The epithelial-to-mesenchymal transition is a key step in the metastatic process by which cancer cells gain the ability to invade tissues and extravasate into the bloodstream. This cellular transformation process, which is associated by morphological change, loss of epithelial traits and gain of mesenchymal markers, is triggered by the secreted cytokine transforming growth factor-β (TGF-β). TGF-β bioactivity is carefully regulated, and its effects on cells are mediated by its receptors on the cell surface. In this review, we first provide a brief overview of major types of glycans, namely, N-glycans, O-glycans, glycosphingolipids and glycosaminoglycans that are involved in cancer progression. Thereafter, we summarize studies on how the glycosylation of TGF-β signaling components regulates TGF-β secretion, bioavailability and TGF-β receptor function. Then, we review glycosylation changes associated with TGF-β-induced epithelial-to-mesenchymal transition in cancer. Identifying and understanding the mechanisms by which glycosylation affects TGF-β signaling and downstream biological responses will facilitate the identification of glycans as biomarkers and enable novel therapeutic approaches.https://doi.org/10.1007/s13238-020-00741-7cancerepithelial-to-mesenchymal transitionglycosphingolipidsN-glycosylationO-glycosylationtransforming growth factor-β |
| spellingShingle | Jing Zhang Peter ten Dijke Manfred Wuhrer Tao Zhang Role of glycosylation in TGF-β signaling and epithelial-to-mesenchymal transition in cancer Protein & Cell cancer epithelial-to-mesenchymal transition glycosphingolipids N-glycosylation O-glycosylation transforming growth factor-β |
| title | Role of glycosylation in TGF-β signaling and epithelial-to-mesenchymal transition in cancer |
| title_full | Role of glycosylation in TGF-β signaling and epithelial-to-mesenchymal transition in cancer |
| title_fullStr | Role of glycosylation in TGF-β signaling and epithelial-to-mesenchymal transition in cancer |
| title_full_unstemmed | Role of glycosylation in TGF-β signaling and epithelial-to-mesenchymal transition in cancer |
| title_short | Role of glycosylation in TGF-β signaling and epithelial-to-mesenchymal transition in cancer |
| title_sort | role of glycosylation in tgf β signaling and epithelial to mesenchymal transition in cancer |
| topic | cancer epithelial-to-mesenchymal transition glycosphingolipids N-glycosylation O-glycosylation transforming growth factor-β |
| url | https://doi.org/10.1007/s13238-020-00741-7 |
| work_keys_str_mv | AT jingzhang roleofglycosylationintgfbsignalingandepithelialtomesenchymaltransitionincancer AT petertendijke roleofglycosylationintgfbsignalingandepithelialtomesenchymaltransitionincancer AT manfredwuhrer roleofglycosylationintgfbsignalingandepithelialtomesenchymaltransitionincancer AT taozhang roleofglycosylationintgfbsignalingandepithelialtomesenchymaltransitionincancer |