title: β-1,4-Galactosyltransferase III enhances invasive phenotypes via β1-integrin and predicts poor prognosis in neuroblastoma.
abstract: OBJECTIVE
  Neuroblastoma (NB) is a neural crest-derived tumor that commonly occurs in childhood. β-1,4-Galactosyltransferase III (B4GALT3) is highly expressed in human fetal brain and is responsible for the generation of poly-N-acetyllactosamine, which plays a critical role in tumor progression. We therefore investigated the expression and role of B4GALT3 in NB.
  
  
  METHODS
  We examined B4GALT3 expression in tumor specimens from 101 NB patients by immunohistochemistry and analyzed the correlation between B4GALT3 expression and clinicopathologic factors or survival. The functional role of B4GALT3 expression was investigated by overexpression or knockdown of B4GALT3 in NB cells for in vitro and in vivo studies.
  
  
  RESULTS
  We found that B4GALT3 expression correlated with advanced clinical stages (P = 0.040), unfavorable Shimada histology (P < 0.001), and lower survival rate (P < 0.001). Multivariate analysis showed that B4GALT3 expression is an independent prognostic factor for poor survival of NB patients. B4GALT3 overexpression increased migration, invasion, and tumor growth of NB cells, whereas B4GALT3 knockdown suppressed the malignant phenotypes of NB cells. Mechanistic investigation showed that B4GALT3-enhanced migration and invasion were significantly suppressed by β1-integrin blocking antibody. Furthermore, B4GALT3 overexpression increased lactosamine glycans on β1-integrin, increased expression of mature β1-integrin via delayed degradation, and enhanced phosphorylation of focal adhesion kinase. Conversely, these properties were decreased by knockdown of B4GALT3 in NB cells.
  
  
  CONCLUSIONS
  Our findings suggest that B4GALT3 predicts an unfavorable prognosis for NB and may regulate invasive phenotypes through modulating glycosylation, degradation, and signaling of β1-integrin in NB cells.
authors: Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, New Taipei City, Taiwan.
authors: Hsiu-Hao
authors: HH
authors: Chang
authors: Chia-Hua
authors: CH
authors: Chen
authors: Chih-Hsing
authors: CH
authors: Chou
authors: Yung-Feng
authors: YF
authors: Liao
authors: Miao-Juei
authors: MJ
authors: Huang
authors: Ya-Hsin
authors: YH
authors: Chen
authors: Wei-Jen
authors: WJ
authors: Wang
authors: John
authors: J
authors: Huang
authors: Ji-Shiang
authors: JS
authors: Hung
authors: Wan-Ling
authors: WL
authors: Ho
authors: Yung-Ming
authors: YM
authors: Jeng
authors: Mei-Ieng
authors: MI
authors: Che
authors: Hsinyu
authors: H
authors: Lee
authors: Meng-Yao
authors: MY
authors: Lu
authors: Yung-Li
authors: YL
authors: Yang
authors: Shiann-Tarng
authors: ST
authors: Jou
authors: Dong-Tsamn
authors: DT
authors: Lin
authors: Kai-Hsin
authors: KH
authors: Lin
authors: Wen-Ming
authors: WM
authors: Hsu
authors: Min-Chuan
authors: MC
authors: Huang
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002675:Child, Preschool; D005260:Female; D005700:Galactosyltransferases / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006031:Glycosylation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D019012:Integrin beta1 / Q000378:metabolism*; D008297:Male; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D010641:Phenotype; D011379:Prognosis; D059748:Proteolysis; D015398:Signal Transduction
chemical_list: D019012:Integrin beta1; D005700:Galactosyltransferases