B3GNT3 expression suppresses cell migration and invasion and predicts favorable outcomes in neuroblastoma

Aberrant expression of the simple mucin-type carbohydrate anti-gens such as T, Tn, sialyl-T and sialyl-Tn is associated with poorprognosis in several cancers. b1,3-N-acetylglucosaminyltransfer-ase-3 (B3GNT3), a member of the b3GlcNAcT family, is responsiblefor forming extended core 1 (T antigen) oligosaccharides. Therole of B3GNT3, which is expressed in various tissues includinghuman fetal brain, in regulating neuroblastoma (NB) formationand cell behaviors remains unclear. Here, we showed thatincreased B3GNT3 expression evaluated using immunohistochem-istry in NB tumor tissues correlated well with the histologicalgrade of differentiation as well as a favorable Shimada’s subsetof pathology. Univariate and multivariate analyses revealed thatpositive B3GNT3 expression in tumor tissues predicted a favor-able prognosis in NB patients independent of other prognosticmarkers. B3GNT3 overexpression suppresses T antigen formationand malignant phenotypes including migration and invasion ofSK-N-SH cells, whereas B3GNT3 knockdown enhances these phe-notypes of SK-N-SH cells. Moreover, B3GNT3 expressiondecreased phosphorylation of focal adhesion kinase (FAK), Src,paxillin, Akt and ERK1⁄2. We conclude that B3GNT3 predicts afavorable cancer behavior of NB and suppresses malignant phe-notypes by modulating mucin-type O-glycosylation and signalingin NB cells. (Cancer Sci, doi: 10.1111/cas.12294, 2013)