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
| Autor: | Zhi-Chao Jia, Xin Wang, Yuan-lian Wan, Jing Zhu, Jianqiang Tang, Yun Dai, Yucun Liu |
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| Rok vydání: | 2011 |
| Předmět: |
Pathology
medicine.medical_specialty Time Factors MAP Kinase Signaling System Proto-Oncogene Proteins c-jun Colorectal cancer Cell Factor VIIa Matrix metalloproteinase p38 Mitogen-Activated Protein Kinases c-Fos Thromboplastin Metastasis Tissue factor Cell Line Tumor medicine Humans Neoplasm Invasiveness Extracellular Signal-Regulated MAP Kinases Promoter Regions Genetic Regulation of gene expression Binding Sites biology business.industry Gastroenterology medicine.disease Up-Regulation Enzyme Activation Gene Expression Regulation Neoplastic Transcription Factor AP-1 medicine.anatomical_structure Cell culture Matrix Metalloproteinase 7 Colonic Neoplasms biology.protein Cancer research business Proto-Oncogene Proteins c-fos Protein Binding |
| Zdroj: | International Journal of Colorectal Disease. 27:437-445 |
| ISSN: | 1432-1262 0179-1958 |
| DOI: | 10.1007/s00384-011-1351-0 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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