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BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

ADAM-17 is a poor prognostic indicator for patients with hilar cholangiocarcinoma and is regulated by FoxM1

Authors: Xiaodong Jiao, Wenlong Yu, Jianxin Qian, Ying Chen, Peilian Wei, Wenzheng Fang, Guanzhen Yu

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

A-disintegrin and metalloproteinases (ADAMs) are members of a family of multidomain transmembrane and secreted proteins. Specific ADAMs are upregulated in human cancers and correlated with tumor progression and poor outcome, but rarely studied in human hilar cholangiocarcinoma (HC). This study aimed to explore the expression profiles of ADAMs and their potential underlying mechanisms promoting cancer progression.

Methods

mRNA expression of ADAM-9, − 10, − 11, − 12, − 15, − 17, − 28, and − 33 was analyzed in human hilar cholangiocarcinoma (HC) samples. Immunohistochemical (IHC) analysis was used to detect the expression of ADAM-10, − 17, − 28, and FoxM1 in HC. The regulation of ADAM-17 by FoxM1 and their functional study was investigated in vivo and in vitro.

Results

ADAM-10, − 17, and − 28 were upregulated in tumors compared with matched non-cancerous tissues. IHC analysis revealed increased expression of ADAM-10, − 17, and − 28 in HC cells, and ADAM17 seems to be an independent prognostic factor. ADAM-17 is regulated by FoxM1. A decrease in the expression of ADAM-17 by silencing FoxM1 led to an inhibition of cell proliferation, tumor growth, and the production of tumor necrosis factor α. IHC analysis showed co-expression of FoxM1 and ADAM-17 in HC specimens.

Conclusions

The findings of the present study show an important role of the cross-talk among FoxM1, ADAM-17, and TNFa in HC development and progression.
Appendix
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Metadata
Title
ADAM-17 is a poor prognostic indicator for patients with hilar cholangiocarcinoma and is regulated by FoxM1
Authors
Xiaodong Jiao
Wenlong Yu
Jianxin Qian
Ying Chen
Peilian Wei
Wenzheng Fang
Guanzhen Yu
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4294-9

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