Pancreatic Cancer Cell Glycosylation Regulates Cell Adhesion and Invasion through the Modulation of alpha 2 beta 1 Integrin and E-Cadherin Function

• Type: Article in International Scientific Journal
• Date: 2014

Authors

Bassaganas, S (Author) Other; Carvalho, S (Author) Other; Dias, AM (Author) Other; Perez Garay, M (Author) Other; Ortiz, MR (Author) Other; Figueras, J (Author) Other; Celso Reis (Author) ICBAS; Pinho, SS (Author) Other; Peracaula, R (Author) Other

Journal

Title: PLoS ONE

Vol. 9 No. 2

Final page: e98595

ISSN: 1932-6203

Publisher: Public Library of Science

Indexing

ISI Web of Knowledge - 44 Citations

Scopus - 45 Citations

Other information

Authenticus ID: P-009-J46

DOI: 10.1371/journal.pone.0098595

Abstract (EN): 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 alpha 2,6-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, alpha 2 beta 1 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 alpha 2,6-sialic acid content on the glycans of their alpha 2 beta 1 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 Ecadherin, which was higher in the ST3Gal III transfectants. In conclusion, changes in the sialylation pattern of alpha 2 beta 1 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 14