Pancreatic Cancer Cell Glycosylation Regulates Cell Adhesion and Invasion through the Modulation of α2β1 Integrin and E-Cadherin Function
| Autor: | Ana M. Dias, M. Rosa Ortiz, Sònia Bassagañas, Celso A. Reis, Marta Pérez-Garay, Salomé S. Pinho, Rosa Peracaula, Joan Figueras, Sandra Carvalho |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Integrins
Glycosylation Cell Membranes Glycobiology lcsh:Medicine Biochemistry Metastasis Collagen receptor chemistry.chemical_compound 0302 clinical medicine Molecular Cell Biology Gastrointestinal Cancers Basic Cancer Research Tumor Cells Cultured Medicine and Health Sciences Phosphorylation lcsh:Science Cell Aggregation Extracellular Matrix Proteins 0303 health sciences Multidisciplinary Organic Compounds Cadherins Cell aggregation Extracellular Matrix Cell biology Chemistry Oncology 030220 oncology & carcinogenesis Physical Sciences Integrin alpha2beta1 Cellular Structures and Organelles Glicosilació Signal Transduction Research Article Integrin Carbohydrates Gastroenterology and Hepatology Biology Collagen Type I Focal adhesion 03 medical and health sciences Cell Adhesion Humans Neoplasm Invasiveness Pancreas -- Cancer Cell adhesion Pàncrees -- Càncer Glycoproteins 030304 developmental biology Cadherin lcsh:R Chemical Compounds Biology and Life Sciences Proteins Membrane Proteins Cell Biology Pancreatic Neoplasms Transmembrane Proteins chemistry Focal Adhesion Protein-Tyrosine Kinases Cancer cell biology.protein lcsh:Q |
| Zdroj: | PLoS ONE PLoS ONE, Vol 9, Iss 5, p e98595 (2014) Recercat. Dipósit de la Recerca de Catalunya instname PLoS One, vol. 9, núm. 5, p. e98595 Articles publicats (D-B) DUGiDocs – Universitat de Girona |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0098595 |
| Popis: | In our previous studies we have described that ST3Gal III transfected pancreatic adenocarcinoma Capan-1 and MDAPanc-28 cells show increased membrane expression levels of sialyl-Lewis x (SLe(x)) along with a concomitant decrease in α2,6-sialic acid compared to control cells. Here we have addressed the role of this glycosylation pattern in the functional properties of two glycoproteins involved in the processes of cancer cell invasion and migration, α2β1 integrin, the main receptor for type 1 collagen, and E-cadherin, responsible for cell-cell contacts and whose deregulation determines cell invasive capabilities. Our results demonstrate that ST3Gal III transfectants showed reduced cell-cell aggregation and increased invasive capacities. ST3Gal III transfected Capan-1 cells exhibited higher SLe(x) and lower α2,6-sialic acid content on the glycans of their α2β1 integrin molecules. As a consequence, higher phosphorylation of focal adhesion kinase tyrosine 397, which is recognized as one of the first steps of integrin-derived signaling pathways, was observed in these cells upon adhesion to type 1 collagen. This molecular mechanism underlies the increased migration through collagen of these cells. In addition, the pancreatic adenocarcinoma cell lines as well as human pancreatic tumor tissues showed colocalization of SLe(x) and E-cadherin, which was higher in the ST3Gal III transfectants. In conclusion, changes in the sialylation pattern of α2β1 integrin and E-cadherin appear to influence the functional role of these two glycoproteins supporting the role of these glycans as an underlying mechanism regulating pancreatic cancer cell adhesion and invasion. |
| Databáze: | OpenAIRE |
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