β-1,4-Galactosyltransferase III enhances invasive phenotypes via β1-integrin and predicts poor prognosis in neuroblastoma

Hsiu Hao Chang, Chia Hua Chen, Chih Hsing Chou, Yung Feng Liao, Miao Juei Huang, Ya Hsin Chen, Wei Jen Wang, John Huang, Ji Shiang Hung, Wan Ling Ho, Yung Ming Jeng, Mei Ieng Che, Hsinyu Lee, Meng Yao Lu, Yung Li Yang, Shiann Tarng Jou, Dong Tsamn Lin, Kai Hsin Lin, Wen Ming Hsu, Min Chuan Huang

研究成果: 雜誌貢獻文章同行評審

38 引文 斯高帕斯(Scopus)

摘要

Purpose: 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. Experimental Design: 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 b1-integrin blocking antibody. Furthermore, B4GALT3 overexpression increased lactosamine glycans on b1-integrin, increased expression of mature b1-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 b1-integrin in NB cells.

原文英語
頁(從 - 到)1705-1716
頁數12
期刊Clinical Cancer Research
19
發行號7
DOIs
出版狀態已發佈 - 4月 1 2013
對外發佈

ASJC Scopus subject areas

  • 腫瘤科
  • 癌症研究

指紋

深入研究「β-1,4-Galactosyltransferase III enhances invasive phenotypes via β1-integrin and predicts poor prognosis in neuroblastoma」主題。共同形成了獨特的指紋。

引用此