B3GNT3 expression suppresses cell migration and invasion and predicts favorable outcomes in neuroblastoma
Journal
Cancer Science
Journal Volume
104
Journal Issue
12
Pages
1600-1608
Date Issued
2013
Author(s)
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. ? 2013 Japanese Cancer Association.
SDGs
Other Subjects
antigen; beta 1,3 n acetylglucosaminyltransferase 3; focal adhesion kinase; mitogen activated protein kinase 1; mitogen activated protein kinase 3; n acetylglucosaminyltransferase; paxillin; protein kinase B; protein tyrosine kinase; unclassified drug; adolescent; article; cell differentiation; cell invasion; cell migration; child; controlled study; enzyme phosphorylation; female; human; human cell; human tissue; immunohistochemistry; infant; major clinical study; male; neuroblastoma; newborn; phenotype; preschool child; priority journal; prognosis; school child; Cell Line, Tumor; Cell Movement; Cell Proliferation; Extracellular Signal-Regulated MAP Kinases; Female; Focal Adhesion Protein-Tyrosine Kinases; Glycosylation; Humans; Male; N-Acetylglucosaminyltransferases; Neoplasm Invasiveness; Neuroblastoma; Paxillin; Prognosis; Proto-Oncogene Proteins c-akt; RNA Interference; RNA, Small Interfering; Signal Transduction; src-Family Kinases; Survival Rate; Transfection; Tumor Markers, Biological
Type
journal article