title: B3GNT3 expression suppresses cell migration and invasion and predicts favorable outcomes in neuroblastoma.
abstract: Aberrant expression of the simple mucin-type carbohydrate antigens such as T, Tn, sialyl-T and sialyl-Tn is associated with poor prognosis in several cancers. β1,3-N-acetylglucosaminyltransferase-3 (B3GNT3), a member of the β3GlcNAcT family, is responsible for forming extended core 1 (T antigen) oligosaccharides. The role of B3GNT3, which is expressed in various tissues including human fetal brain, in regulating neuroblastoma (NB) formation and cell behaviors remains unclear. Here, we showed that increased B3GNT3 expression evaluated using immunohistochemistry in NB tumor tissues correlated well with the histological grade of differentiation as well as a favorable Shimada's subset of pathology. Univariate and multivariate analyses revealed that positive B3GNT3 expression in tumor tissues predicted a favorable prognosis in NB patients independent of other prognostic markers. B3GNT3 overexpression suppresses T antigen formation and malignant phenotypes including migration and invasion of SK-N-SH cells, whereas B3GNT3 knockdown enhances these phenotypes of SK-N-SH cells. Moreover, B3GNT3 expression decreased phosphorylation of focal adhesion kinase (FAK), Src, paxillin, Akt and ERK1/2. We conclude that B3GNT3 predicts a favorable cancer behavior of NB and suppresses malignant phenotypes by modulating mucin-type O-glycosylation and signaling in NB cells.
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Pediatrics, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
authors.forename: Wan-ling
authors.initials: WL
authors.lastname: Ho
authors.forename: Mei-Ieng
authors.initials: MI
authors.lastname: Che
authors.forename: Chih-Hsing
authors.initials: CH
authors.lastname: Chou
authors.forename: Hsiu-Hao
authors.initials: HH
authors.lastname: Chang
authors.forename: Yung-Ming
authors.initials: YM
authors.lastname: Jeng
authors.forename: Wen-Ming
authors.initials: WM
authors.lastname: Hsu
authors.forename: Kai-Hsin
authors.initials: KH
authors.lastname: Lin
authors.forename: Min-Chuan
authors.initials: MC
authors.lastname: Huang
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D008297:Male; D017351:N-Acetylglucosaminyltransferases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009447:Neuroblastoma / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D051419:Paxillin / Q000378:metabolism; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction; D015996:Survival Rate; D014162:Transfection; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D051419:Paxillin; D034741:RNA, Small Interfering; D017351:N-Acetylglucosaminyltransferases; C428133:beta-1,3-N--acetylglucosaminyltransferase T3; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases