北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 北京大学第一临床医学院  > 期刊论文
学科主题: 临床医学
题名:
Tissue factor/activated factor VIIa induces matrix metalloproteinase-7 expression through activation of c-Fos via ERK1/2 and p38 MAPK signaling pathways in human colon cancer cell
作者: Jia, Zhi-Chao; Wan, Yuan-Lian; Tang, Jian-Qiang; Dai, Yun; Liu, Yu-Cun; Wang, Xin; Zhu, Jing
关键词: Colorectal cancer ; Tissue factor ; Factor VIIa c-Fos ; MMP-7
刊名: INTERNATIONAL JOURNAL OF COLORECTAL DISEASE
发表日期: 2012-04-01
DOI: 10.1007/s00384-011-1351-0
卷: 27, 期:4, 页:437-445
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Gastroenterology & Hepatology ; Surgery
研究领域[WOS]: Gastroenterology & Hepatology ; Surgery
关键词[WOS]: COLORECTAL-CANCER ; MATRILYSIN EXPRESSION ; PANCREATIC-CANCER ; TUMOR PROGRESSION ; POOR-PROGNOSIS ; ANGIOGENESIS ; CARCINOMA ; INVASION ; MMP-7 ; MATRIX-METALLOPROTEINASE-7
英文摘要:

Increased expression of tissue factor (TF) is associated with tumor invasion and metastasis in human colorectal cancer. We have previously observed that TF/FVIIa upregulates matrix metalloproteinase-7 (MMP-7) expression at the transcriptional level in colon cancer cells. MMP-7 overexpression is believed to play an important role in tumor invasion and metastasis. The aim of this study is to elucidate the molecular mechanisms by which TF/FVIIa induced MMP-7 expression and cell invasion in vitro.

Reverse transcription polymerase chain reaction, Western blot, luciferase assay, and chromatin immunoprecipitation (ChIP) were used to determine the potential mechanism and signaling pathways by which TF/FVIIa induced MMP-7 expression and cell invasion in LoVo cells. Small interfering RNA (siRNA) and cell invasion assay was used to examine whether blocking c-Fos expression could abolish FVIIa-mediated upregulation of MMP-7 and cell invasion in vitro.

The results showed that FVIIa induced the upregulation of MMP-7 both at the mRNA and protein levels in a time- and dose-dependent manner and increased the invasive behavior of LoVo cells. FVIIa enhanced the promoter activity of MMP-7, and the activator protein-1 (AP-1) binding site was responsible for the activation. Site mutation of the AP-1 binding site in the promoter almost completely abolished FVIIa-mediated response. Furthermore, ChIP assay confirmed that FVIIa promoted the direct binding of c-Fos with the MMP-7 promoter in vivo. FVIIa also induced the expression and nuclear accumulation of the AP-1 subunit c-Fos. siRNA-mediated knockdown of c-Fos eliminated FVIIa-stimulated MMP-7 expression and cell migration in vitro. In addition, selective mitogen-activated protein kinase (MAPK) kinase (MEK1/2) inhibitor (PD98059) and p38 MAPK inhibitor SB203580 suppressed MMP-7 upregulation induced by FVIIa.

Our data suggest that a novel TF/FVIIa/MAPK/c-Fos/MMP-7 axis plays an important role in modulating the invasion of colon cancer cells and blockage of this pathway holds promise to treat colon cancer metastasis.

语种: 英语
所属项目编号: 30872469 ; 30801092
项目资助者: National Natural Sciences Foundation of China ; National Natural Sciences Youth Foundation of China ; "985" Project Foundation of Peking University
WOS记录号: WOS:000301777100003
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/61009
Appears in Collections:北京大学第一临床医学院_期刊论文

Files in This Item:

There are no files associated with this item.


作者单位: Peking Univ, Lab Colon Canc, Hosp 1, Beijing 100034, Peoples R China

Recommended Citation:
Jia, Zhi-Chao,Wan, Yuan-Lian,Tang, Jian-Qiang,et al. Tissue factor/activated factor VIIa induces matrix metalloproteinase-7 expression through activation of c-Fos via ERK1/2 and p38 MAPK signaling pathways in human colon cancer cell[J]. INTERNATIONAL JOURNAL OF COLORECTAL DISEASE,2012,27(4):437-445.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Jia, Zhi-Chao]'s Articles
[Wan, Yuan-Lian]'s Articles
[Tang, Jian-Qiang]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Jia, Zhi-Chao]‘s Articles
[Wan, Yuan-Lian]‘s Articles
[Tang, Jian-Qiang]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  北京大学医学部 - Feedback
Powered by CSpace