title: Pancreatic cancer cell glycosylation regulates cell adhesion and invasion through the modulation of α2β1 integrin and E-cadherin function.
abstract: 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.
authors.affiliation: Biochemistry and Molecular Biology Unit, Department of Biology, University of Girona, Girona, Spain.
authors.forename: Sònia
authors.initials: S
authors.lastname: Bassagañas
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal; Institute of Biomedical Sciences of Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
authors.forename: Sandra
authors.initials: S
authors.lastname: Carvalho
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal; Institute of Biomedical Sciences of Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Dias
authors.affiliation: Biochemistry and Molecular Biology Unit, Department of Biology, University of Girona, Girona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Pérez-Garay
authors.affiliation: Department of Pathology, Dr. Josep Trueta University Hospital, Girona, Spain.
authors.forename: M Rosa
authors.initials: MR
authors.lastname: Ortiz
authors.affiliation: Department of Surgery, Dr. Josep Trueta University Hospital, IdIBGi, Girona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Figueras
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal; Institute of Biomedical Sciences of Abel Salazar (ICBAS), University of Porto, Porto, Portugal; Medical Faculty, University of Porto, Porto, Portugal.
authors.forename: Celso A
authors.initials: CA
authors.lastname: Reis
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal; Institute of Biomedical Sciences of Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
authors.forename: Salomé S
authors.initials: SS
authors.lastname: Pinho
authors.affiliation: Biochemistry and Molecular Biology Unit, Department of Biology, University of Girona, Girona, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Peracaula
mesh_terms: D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D002449:Cell Aggregation / Q000502:physiology; D024042:Collagen Type I / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D038982:Integrin alpha2beta1 / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D010766:Phosphorylation / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014407:Tumor Cells, Cultured
chemical_list: D015820:Cadherins; D024042:Collagen Type I; D038982:Integrin alpha2beta1; D051416:Focal Adhesion Protein-Tyrosine Kinases