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学科主题临床医学
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
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
2012-04-01
DOI10.1007/s00384-011-1351-0
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
WOS记录号WOS:000301777100003
项目编号30872469 ; 30801092
资助机构National Natural Sciences Foundation of China ; National Natural Sciences Youth Foundation of China ; "985" Project Foundation of Peking University
引用统计
被引频次:15[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/61009
专题北京大学第一临床医学院
北京大学第一临床医学院_普通外科
北京大学第一临床医学院_消化科
作者单位Peking Univ, Lab Colon Canc, Hosp 1, Beijing 100034, Peoples R China
推荐引用方式
GB/T 7714
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.
APA Jia, Zhi-Chao.,Wan, Yuan-Lian.,Tang, Jian-Qiang.,Dai, Yun.,Liu, Yu-Cun.,...&Zhu, Jing.(2012).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.INTERNATIONAL JOURNAL OF COLORECTAL DISEASE,27(4),437-445.
MLA Jia, Zhi-Chao,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".INTERNATIONAL JOURNAL OF COLORECTAL DISEASE 27.4(2012):437-445.
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