Oncotarget

Research Papers:

Mucin1 promotes the migration and invasion of hepatocellular carcinoma cells via JNK-mediated phosphorylation of Smad2 at the C-terminal and linker regions

Juan Wang, Guomu Liu, Qiongshu Li, Fang Wang, Fei Xie, Ruiping Zhai, Yingying Guo, Tanxiu Chen, Nannan Zhang, Weihua Ni, Hongyan Yuan and Guixiang Tai _

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Oncotarget. 2015; 6:19264-19278. https://doi.org/10.18632/oncotarget.4267

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Abstract

Juan Wang1, Guomu Liu1, Qiongshu Li1, Fang Wang1, Fei Xie1, Ruiping Zhai1, Yingying Guo1, Tanxiu Chen1, Nannan Zhang1, Weihua Ni1, Hongyan Yuan1 and Guixiang Tai1

1 Department of Immunology, College of Basic Medical Science, Jilin University, Changchun, China

Correspondence to:

Guixiang Tai, email:

Keywords: Mucin1, HCC, JNK, TGF-β, Smad2L/C

Received: March 20, 2015 Accepted: May 13, 2015 Published: May 25, 2015

Abstract

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.


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