Mucin1 promotes the migration and invasion of hepatocellular carcinoma cells via JNK-mediated phosphorylation of Smad2 at the C-terminal and linker regions
| Autor: | Fang Wang, Guixiang Tai, Qiongshu Li, Ruiping Zhai, Guomu Liu, Nannan Zhang, Yingying Guo, Hongyan Yuan, Tanxiu Chen, Fei Xie, Weihua Ni, Juan Wang |
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| Rok vydání: | 2015 |
| Předmět: |
TGF-β
Carcinoma Hepatocellular MAP Kinase Signaling System Smad2 Protein Matrix metalloproteinase Transfection Cell Movement Cell Line Tumor Humans Gene silencing Phosphorylation HCC Autocrine signalling neoplasms Mucin1 biology Oncogene Liver Neoplasms Mucin-1 Cell migration Hep G2 Cells Transforming growth factor beta Smad2L/C digestive system diseases Oncology Immunology biology.protein Cancer research JNK Research Paper Transforming growth factor |
| Zdroj: | Scopus-Elsevier Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.4267 |
| Popis: | Mucin1 (MUC1), as an oncogene, plays a key role in the progression and tumorigenesis of many human adenocarcinomas. In this study, wound-healing, transwell migration and matrigel invasion assays showed that MUC1 promotes human hepatocellular carcinoma (HCC) cell migration and invasion by MUC1 gene silencing and overexpressing. Treatment with exogenous transforming growth factor beta (TGF-β)1, TGF-β type I receptor (TβRI) inhibitor, TGF-β1 siRNAs, or activator protein 1 (AP-1) inhibitor to MUC1-overexpressing HCC cells revealed that MUC1-induced autocrine TGF-β via JNK/AP-1 pathway promotes the cell migration and invasion. In addition, the migration and invasion of HCC cells were more significantly inhibited by JNK inhibitor compared with that by TβRI inhibitor or TGF-β1 siRNAs. Further studies demonstrated that MUC1-mediated JNK activation not only enhances the phosphorylation of Smad2 C-terminal at Ser-465/467 site (Smad2C) through TGF-β/TβRI, but also directly enhances the phosphorylation of Smad2 linker region at Ser-245/250/255 site (Smad2L), and then both of them collaborate to upregulate matrix metalloproteinase (MMP)-9-mediated cell migration and invasion of HCC. These results indicate that MUC1 is an attractive target in liver cancer therapy. |
| Databáze: | OpenAIRE |
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