title: Mucin1 promotes the migration and invasion of hepatocellular carcinoma cells via JNK-mediated phosphorylation of Smad2 at the C-terminal and linker regions.
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.
authors.affiliation: Department of Immunology, College of Basic Medical Science, Jilin University, Changchun, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Immunology, College of Basic Medical Science, Jilin University, Changchun, China.
authors.forename: Guomu
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Immunology, College of Basic Medical Science, Jilin University, Changchun, China.
authors.forename: Qiongshu
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Immunology, College of Basic Medical Science, Jilin University, Changchun, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Immunology, College of Basic Medical Science, Jilin University, Changchun, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xie
authors.affiliation: Department of Immunology, College of Basic Medical Science, Jilin University, Changchun, China.
authors.forename: Ruiping
authors.initials: R
authors.lastname: Zhai
authors.affiliation: Department of Immunology, College of Basic Medical Science, Jilin University, Changchun, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Immunology, College of Basic Medical Science, Jilin University, Changchun, China.
authors.forename: Tanxiu
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Immunology, College of Basic Medical Science, Jilin University, Changchun, China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Immunology, College of Basic Medical Science, Jilin University, Changchun, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Ni
authors.affiliation: Department of Immunology, College of Basic Medical Science, Jilin University, Changchun, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Department of Immunology, College of Basic Medical Science, Jilin University, Changchun, China.
authors.forename: Guixiang
authors.initials: G
authors.lastname: Tai
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System; D018396:Mucin-1 / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: C060192:MUC1 protein, human; D018396:Mucin-1; C497782:SMAD2 protein, human; D051899:Smad2 Protein
keywords: HCC; JNK; Mucin1; Smad2L/C; TGF-β