Upregulation of endocan by epstein-barr virus latent membrane protein 1 and its clinical significance in nasopharyngeal Carcinoma

Ping Hung Yu, Shu Fan Chou, Chi Long Chen, Hung Hung, Ching Yu Lai, Pei Ming Yang, Yung Ming Jeng, Shwu Fang Liaw, Huan Hsien Kuo, Hey Chi Hsu, Jen Yang Chen, Won Bo Wang

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Abstract

Abstract Endocan (or called Esm-1) has been shown to have tumorigenic activities and its expression is associated with poor prognosis in various cancers. Latent membrane protein 1 (LMP1) is an Epstein-Barr virus (EBV)-encoded oncoprotein and has been shown to play an important role in the pathogenesis of EBV-associated nasopharyngeal carcinoma (NPC). To further understand the role of LMP1 in the pathogenesis of NPC, microarray analysis of LMP1- regulated genes in epithelial cells was performed. We found that endocan was one of the major cellular genes upregulated by LMP1. This induction of endocan by LMP1 was confirmed in several epithelial cell lines including an NPC cell line. Upregulation of endocan by LMP1 was found to be mediated through the CTAR1 and CTAR2 domains of LMP1 and through the LMP1-activated NF-?B, MEK-ERK and JNK signaling pathways. To study whether endocan was expressed in NPC and whether endocan expression was associated with LMP1 expression in NPC, the expression of endocan and LMP1 in tumor tissues from 42 NPC patients was evaluated by immunohistochemistry. Expression of endocan was found in 52% of NPC specimens. Significant correlation between LMP1 and endocan expression was observed (p0.0001). Moreover, NPC patients with endocan expression were found to have a shorter survival than NPC patients without endocan expression (p=0.0104, log-rank test). Univariate and Multivariate analyses revealed that endocan was a potential prognostic factor for NPC. Finally, we demonstrated that endocan could stimulate the migration and invasion ability of endothelial cells and this activity of endocan was dependent on the glycan moiety and the phenylalanine-rich region of endocan. Together, these studies not only identify a new molecular marker that may predict the survival of NPC patients but also provide a new insight to the pathogenesis of NPC.

Original languageEnglish
Article numbere82254
JournalPLoS One
Volume8
Issue number12
DOIs
Publication statusPublished - Dec 5 2013

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Human herpesvirus 4
membrane proteins
carcinoma
Membrane Proteins
Up-Regulation
pathogenesis
Viruses
Epstein-Barr virus EBV-associated membrane antigen
Nasopharyngeal carcinoma
Genes
epithelial cells
Epithelial Cells
cell lines
Cell Line
Oncogene Proteins
Mitogen-Activated Protein Kinase Kinases
Endothelial cells
neoplasms
Survival
MAP Kinase Signaling System

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Upregulation of endocan by epstein-barr virus latent membrane protein 1 and its clinical significance in nasopharyngeal Carcinoma. / Yu, Ping Hung; Chou, Shu Fan; Chen, Chi Long; Hung, Hung; Lai, Ching Yu; Yang, Pei Ming; Jeng, Yung Ming; Liaw, Shwu Fang; Kuo, Huan Hsien; Hsu, Hey Chi; Chen, Jen Yang; Wang, Won Bo.

In: PLoS One, Vol. 8, No. 12, e82254, 05.12.2013.

Research output: Contribution to journalArticle

Yu, Ping Hung ; Chou, Shu Fan ; Chen, Chi Long ; Hung, Hung ; Lai, Ching Yu ; Yang, Pei Ming ; Jeng, Yung Ming ; Liaw, Shwu Fang ; Kuo, Huan Hsien ; Hsu, Hey Chi ; Chen, Jen Yang ; Wang, Won Bo. / Upregulation of endocan by epstein-barr virus latent membrane protein 1 and its clinical significance in nasopharyngeal Carcinoma. In: PLoS One. 2013 ; Vol. 8, No. 12.
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abstract = "Abstract Endocan (or called Esm-1) has been shown to have tumorigenic activities and its expression is associated with poor prognosis in various cancers. Latent membrane protein 1 (LMP1) is an Epstein-Barr virus (EBV)-encoded oncoprotein and has been shown to play an important role in the pathogenesis of EBV-associated nasopharyngeal carcinoma (NPC). To further understand the role of LMP1 in the pathogenesis of NPC, microarray analysis of LMP1- regulated genes in epithelial cells was performed. We found that endocan was one of the major cellular genes upregulated by LMP1. This induction of endocan by LMP1 was confirmed in several epithelial cell lines including an NPC cell line. Upregulation of endocan by LMP1 was found to be mediated through the CTAR1 and CTAR2 domains of LMP1 and through the LMP1-activated NF-?B, MEK-ERK and JNK signaling pathways. To study whether endocan was expressed in NPC and whether endocan expression was associated with LMP1 expression in NPC, the expression of endocan and LMP1 in tumor tissues from 42 NPC patients was evaluated by immunohistochemistry. Expression of endocan was found in 52{\%} of NPC specimens. Significant correlation between LMP1 and endocan expression was observed (p0.0001). Moreover, NPC patients with endocan expression were found to have a shorter survival than NPC patients without endocan expression (p=0.0104, log-rank test). Univariate and Multivariate analyses revealed that endocan was a potential prognostic factor for NPC. Finally, we demonstrated that endocan could stimulate the migration and invasion ability of endothelial cells and this activity of endocan was dependent on the glycan moiety and the phenylalanine-rich region of endocan. Together, these studies not only identify a new molecular marker that may predict the survival of NPC patients but also provide a new insight to the pathogenesis of NPC.",
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AU - Chou, Shu Fan

AU - Chen, Chi Long

AU - Hung, Hung

AU - Lai, Ching Yu

AU - Yang, Pei Ming

AU - Jeng, Yung Ming

AU - Liaw, Shwu Fang

AU - Kuo, Huan Hsien

AU - Hsu, Hey Chi

AU - Chen, Jen Yang

AU - Wang, Won Bo

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AB - Abstract Endocan (or called Esm-1) has been shown to have tumorigenic activities and its expression is associated with poor prognosis in various cancers. Latent membrane protein 1 (LMP1) is an Epstein-Barr virus (EBV)-encoded oncoprotein and has been shown to play an important role in the pathogenesis of EBV-associated nasopharyngeal carcinoma (NPC). To further understand the role of LMP1 in the pathogenesis of NPC, microarray analysis of LMP1- regulated genes in epithelial cells was performed. We found that endocan was one of the major cellular genes upregulated by LMP1. This induction of endocan by LMP1 was confirmed in several epithelial cell lines including an NPC cell line. Upregulation of endocan by LMP1 was found to be mediated through the CTAR1 and CTAR2 domains of LMP1 and through the LMP1-activated NF-?B, MEK-ERK and JNK signaling pathways. To study whether endocan was expressed in NPC and whether endocan expression was associated with LMP1 expression in NPC, the expression of endocan and LMP1 in tumor tissues from 42 NPC patients was evaluated by immunohistochemistry. Expression of endocan was found in 52% of NPC specimens. Significant correlation between LMP1 and endocan expression was observed (p0.0001). Moreover, NPC patients with endocan expression were found to have a shorter survival than NPC patients without endocan expression (p=0.0104, log-rank test). Univariate and Multivariate analyses revealed that endocan was a potential prognostic factor for NPC. Finally, we demonstrated that endocan could stimulate the migration and invasion ability of endothelial cells and this activity of endocan was dependent on the glycan moiety and the phenylalanine-rich region of endocan. Together, these studies not only identify a new molecular marker that may predict the survival of NPC patients but also provide a new insight to the pathogenesis of NPC.

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