title: Expression of GALNT2 in human extravillous trophoblasts and its suppressive role in trophoblast invasion.
abstract: Extravillus trophoblast (EVT) invasion plays a critical role in placental development. Integrins bind to extracellular matrix (ECM) proteins to mediate EVT cell adhesion, migration, and invasion. Changes in O-glycans on β1-integrin have been found to regulate cancer cell behavior. We hypothesize that O-glycosyltransferases can regulate EVT invasion through modulating the glycosylation and function of β1-integrin. Here, we found that the GALNT1 and GALNT2 mRNA were highly expressed in HTR8/SVneo and first trimester EVT cells. Immunohistochemstry and immunofluorescence staining showed that GALNT2 was expressed in subpopulations of EVT cells in deciduas, but not in syncytiotrophoblasts and cytotrophoblasts of placental villi. The percentage of GALNT2-positive EVT cells increased with gestational ages. Overexpression of GALNT2 in HTR8/SVneo cells significantly enhanced cell-collagen IV adhesion, but suppressed cell migration and invasion. Notably, we found that GALNT2 increased the expression of Tn antigen (GalNAc-Ser/Thr) on β1-integrin as revealed by Vicia Villosa agglutinin (VVA) binding. Furthermore, GALNT2 suppressed the phosphorylation of focal adhesion kinase (FAK), a crucial downstream signaling molecule of β1-integrin. Our findings suggest that GALNT2 is a critical initiating enzyme of O-glycosylation for regulating EVT invasion.
authors.affiliation: Department of Anatomy, Faculty of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: W-C
authors.initials: WC
authors.lastname: Liao
authors.forename: C-H
authors.initials: CH
authors.lastname: Chen
authors.forename: C-H
authors.initials: CH
authors.lastname: Liu
authors.forename: M-J
authors.initials: MJ
authors.lastname: Huang
authors.forename: C-W
authors.initials: CW
authors.lastname: Chen
authors.forename: J-S
authors.initials: JS
authors.lastname: Hung
authors.forename: C-H
authors.initials: CH
authors.lastname: Chou
authors.forename: C-H
authors.initials: CH
authors.lastname: Chen
authors.forename: M-I
authors.initials: MI
authors.lastname: Che
authors.forename: H-M
authors.initials: HM
authors.lastname: Chang
authors.forename: C-T
authors.initials: CT
authors.lastname: Lan
authors.forename: H-C
authors.initials: HC
authors.lastname: Huang
authors.forename: G-F
authors.initials: GF
authors.lastname: Tseng
authors.forename: M-K
authors.initials: MK
authors.lastname: Shyu
authors.forename: M-C
authors.initials: MC
authors.lastname: Huang
mesh_terms: D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D002478:Cells, Cultured; D003656:Decidua / Q000166:cytology / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006031:Glycosylation; D006801:Humans; D039641:Integrin beta Chains / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D017350:N-Acetylgalactosaminyltransferases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D010929:Placentation; D011247:Pregnancy; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism*; D000097763:Polypeptide N-acetylgalactosaminyltransferase
chemical_list: D051416:Focal Adhesion Protein-Tyrosine Kinases; D039641:Integrin beta Chains; D007527:Isoenzymes; D017350:N-Acetylgalactosaminyltransferases; D011994:Recombinant Proteins; D000097763:Polypeptide N-acetylgalactosaminyltransferase