Open AccessB3 GNT 3 expression suppresses cell migration and invasion and predicts favorable outcomes in neuroblastoma
Author(s) -
Ho WanLing,
Che MeiIeng,
Chou ChihHsing,
Chang HsiuHao,
Jeng YungMing,
Hsu WenMing,
Lin KaiHsin,
Huang MinChuan
Publication year - 2013
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12294
Subject(s) - cancer research , antigen , gene knockdown , mucin , neuroblastoma , phenotype , biology , immunohistochemistry , focal adhesion , paxillin , pathology , microbiology and biotechnology , phosphorylation , cell culture , medicine , immunology , gene , biochemistry , genetics
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 (B3 GNT 3), a member of the β3Glc NA cT family, is responsible for forming extended core 1 (T antigen) oligosaccharides. The role of B3 GNT 3, 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 B3 GNT 3 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 B3 GNT 3 expression in tumor tissues predicted a favorable prognosis in NB patients independent of other prognostic markers. B3 GNT 3 overexpression suppresses T antigen formation and malignant phenotypes including migration and invasion of SK ‐N‐ SH cells, whereas B3 GNT 3 knockdown enhances these phenotypes of SK ‐N‐ SH cells. Moreover, B3 GNT 3 expression decreased phosphorylation of focal adhesion kinase ( FAK ), Src, paxillin, Akt and ERK 1/2. We conclude that B3 GNT 3 predicts a favorable cancer behavior of NB and suppresses malignant phenotypes by modulating mucin‐type O ‐glycosylation and signaling in NB cells.