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

doi:10.1158/1078-0432.CCR-12-2367

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

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Abstract

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.

Original language	English
Pages (from-to)	1705-1716
Number of pages	12
Journal	Clinical Cancer Research
Volume	19
Issue number	7
DOIs	https://doi.org/10.1158/1078-0432.CCR-12-2367
Publication status	Published - Apr 1 2013
Externally published	Yes

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1158/1078-0432.CCR-12-2367

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Chang, H. H., Chen, C. H., Chou, C. H., Liao, Y. F., Huang, M. J., Chen, Y. H., Wang, W. J., Huang, J., Hung, J. S., Ho, W. L., Jeng, Y. M., Che, M. I., Lee, H., Lu, M. Y., Yang, Y. L., Jou, S. T., Lin, D. T., Lin, K. H., Hsu, W. M., & Huang, M. C. (2013). β-1,4-Galactosyltransferase III enhances invasive phenotypes via β1-integrin and predicts poor prognosis in neuroblastoma. Clinical Cancer Research, 19(7), 1705-1716. https://doi.org/10.1158/1078-0432.CCR-12-2367

Chang, HH, Chen, CH, Chou, CH, Liao, YF, Huang, MJ, Chen, YH, Wang, WJ, Huang, J, Hung, JS, Ho, WL, Jeng, YM, Che, MI, Lee, H, Lu, MY, Yang, YL, Jou, ST, Lin, DT, Lin, KH, Hsu, WM & Huang, MC 2013, 'β-1,4-Galactosyltransferase III enhances invasive phenotypes via β1-integrin and predicts poor prognosis in neuroblastoma', Clinical Cancer Research, vol. 19, no. 7, pp. 1705-1716. https://doi.org/10.1158/1078-0432.CCR-12-2367

@article{d8e210cfb5c947d9b627ed7203182c03,

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

abstract = "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.",

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

year = "2013",

month = apr,

day = "1",

doi = "10.1158/1078-0432.CCR-12-2367",

language = "English",

volume = "19",

pages = "1705--1716",

journal = "Clinical Cancer Research",

issn = "1078-0432",

publisher = "American Association for Cancer Research Inc.",

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TY - JOUR

T1 - β-1,4-Galactosyltransferase III enhances invasive phenotypes via β1-integrin and predicts poor prognosis in neuroblastoma

AU - Chang, Hsiu Hao

AU - Chen, Chia Hua

AU - Chou, Chih Hsing

AU - Liao, Yung Feng

AU - Huang, Miao Juei

AU - Chen, Ya Hsin

AU - Wang, Wei Jen

AU - Huang, John

AU - Hung, Ji Shiang

AU - Ho, Wan Ling

AU - Jeng, Yung Ming

AU - Che, Mei Ieng

AU - Lee, Hsinyu

AU - Lu, Meng Yao

AU - Yang, Yung Li

AU - Jou, Shiann Tarng

AU - Lin, Dong Tsamn

AU - Lin, Kai Hsin

AU - Hsu, Wen Ming

AU - Huang, Min Chuan

PY - 2013/4/1

Y1 - 2013/4/1

N2 - 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.

AB - 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.

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U2 - 10.1158/1078-0432.CCR-12-2367

DO - 10.1158/1078-0432.CCR-12-2367

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AN - SCOPUS:84877091745

SN - 1078-0432

VL - 19

SP - 1705

EP - 1716

JO - Clinical Cancer Research

JF - Clinical Cancer Research

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ER -

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

Abstract

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