B4GALNT3 expression predicts a favorable prognosis and suppresses cell migration and invasion via β 1 integrin signaling in neuroblastoma
Journal
American Journal of Pathology
Journal Volume
179
Journal Issue
3
Pages
1394-1404
Date Issued
2011
Author(s)
Che M.-I.
Liao Y.-F.
Chen C.-H.
Huang Y.-M.
Quon M.J.
Lee H.
Huang H.-C.
Abstract
β1,4-N-acetylgalactosaminyltransferase III (B4GALNT3) promotes the formation of GalNAcβ1,4GlcNAc (LacdiNAc or LDN). Drosophila β1,4-N-acetylgalactosaminyltransferase A (B4GALNTA) contributes to the synthesis of LDN, which helps regulate neuronal development. In this study, we investigated the expression and role of B4GALNT3 in human neuroblastoma (NB). We used IHC analysis to examine 87 NB tumors, and we identified correlations between B4GALNT3 expression and clinicopathologic factors, including patient survival. Effects of recombinant B4GALNT3 on cell behavior and signaling were studied in SK-N-SH and SH-SY5Y NB cells. Increased expression of B4GALNT3 in NB tumors correlated with a favorable histologic profile (P < 0.001, χ 2 test) and early clinical staging (P = 0.041, χ 2 test) and was a favorable prognostic factor for survival as evaluated by univariate and multivariate analyses. Reexpression of B4GALNT3 in SK-N-SH and SH-SY5Y cells suppressed cell proliferation, colony formation, migration, and invasion. Moreover, B4GALNT3 increased the LacdiNAc modification of β 1 integrin, leading to decreased phosphorylation of focal adhesion kinase (FAK), Src, paxillin, Akt, and ERK1/2. B4GALNT3-mediated suppression of cell migration and invasion were substantially reversed by concomitant expression of constitutively active Akt or MEK. We conclude that B4GALNT3 predicts a favorable prognosis for NB and suppresses the malignant phenotype via decreasing β 1 integrin signaling. ? 2011 American Society for Investigative Pathology.
SDGs
Other Subjects
beta1 integrin; beta1,4 n acetylgalactosaminyltransferase III; focal adhesion kinase; glycosyltransferase; unclassified drug; adult; article; cancer staging; cancer survival; cell function; cell invasion; cell migration; cell proliferation; controlled study; enzyme inhibition; enzyme phosphorylation; female; genetic transfection; histopathology; human; human cell; human tissue; immunoblotting; immunohistochemistry; immunoprecipitation; major clinical study; male; nerve cell differentiation; neuroblastoma; prediction; priority journal; prognosis; protein expression; signal transduction; Antigens, CD29; Antineoplastic Agents; Cell Line, Tumor; Cell Movement; Cell Survival; Cell Transformation, Neoplastic; Child; Child, Preschool; Female; Humans; Male; N-Acetylgalactosaminyltransferases; Neoplasm Invasiveness; Neuroblastoma; Prognosis; Signal Transduction; Tretinoin; Tumor Markers, Biological
Type
journal article