title: Specific N-glycan alterations are coupled in epithelial-mesenchymal transition induced by EGF in GE11 epithelial cells.
abstract: Epithelial-mesenchymal transition (EMT) is a phenomenon in cancer progression during which cancer cells undergo remarkable alteration acquiring highly invasive property. The aim of this study was to evaluate specific N-glycan alterations during EMT induced by epidermal growth factor (EGF) in GE11 epithelial cells. Herein, we demonstrated that EGF activated epidermal growth factor receptor (EGFR)/Akt/extracellular signal-regulated kinase (ERK) phosphorylation and promoted GE11 cell proliferation. Meanwhile, EGF stimulated the epithelial cells to undergo morphological alteration, destroying cell-cell inter-contact and exhibiting mesenchymal cells higher metastatic potential. A wound-healing assay showed the migratory ability increased 1.5-fold after EGF treatment. Moreover, the relative intensity of N-cadherin versus E-cadherin increased 2.6-fold, and the E-cadherin distribution in cell-cell junctions became jagged and faint after EGF incubation for 72 h. Interestingly, the amounts of bisecting GlcNAc structure were dramatically declined, by contrast, the formation of β1,6 GlcNAc branches on cell surface was upregulated during EMT induced by EGF. To understand the roles of N-glycans in EGF-induced EMT, the cells were stably transfected with N-acetylglucosaminyltransferase III (GnT-III), which catalyzes the bisecting GlcNAc structure formation. As the markers for EMT, EGF-induced E-cadherin decrease and fibronectin increase were delayed in GnT-III-overexpressing cells. Taken together, these results demonstrated that specific N-glycan alterations were coupled in EMT induced by EGF, which might be contributed to diagnosis and therapy of tumor metastasis.
authors.affiliation: College of Fisheries and Life Science, Dalian Ocean University, Dalian, 116023, China.|Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi, 981-8558, Japan.
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Xu
authors.affiliation: College of Fisheries and Life Science, Dalian Ocean University, Dalian, 116023, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Qu
authors.affiliation: Dalian Elite Analytical Instruments Company Limited, Dalian, 116023, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Wang
authors.affiliation: Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi, 981-8558, Japan.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Gu
authors.affiliation: Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, China.
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Du
authors.affiliation: College of Fisheries and Life Science, Dalian Ocean University, Dalian, 116023, China.
authors.forename: Linsheng
authors.initials: L
authors.lastname: Song
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D066246:ErbB Receptors / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005434:Flow Cytometry; D037102:Lectins / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011134:Polysaccharides / Q000032:analysis / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D015820:Cadherins; D005353:Fibronectins; D037102:Lectins; D011134:Polysaccharides; D004815:Epidermal Growth Factor; D017351:N-Acetylglucosaminyltransferases; C054599:beta-1,4-mannosyl-glycoprotein beta-1,4-N-acetylglucosaminyltransferase; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: N-glycan; bisecting GlcNAc; epidermal growth factor; epithelial-mesenchymal transition; metastasis; tumorigenesis