title: Reduced N-acetylglucosaminyltransferase III expression via Smad3 and Erk signaling in TGF-β1-induced HCC EMT model.
abstract: N-acetylglucosaminyltransferase III (GnT-III), encoded by the MGAT3 glycogene, is thought to be a tumor metastatic suppressor. Our previous studies found that the mRNA expression level of GnT-III decreased in a hepatocyte growth factor (HGF)-induced hepatocellular carcinoma (HCC) epithelial-mesenchymal transition (EMT) model. However, the molecular mechanism of GnT-III expression is unclear. In the present study, we established an HCC EMT model using the classic inducer transforming growth factor-β1 (TGF-β1) and focused on the Smad3 and Erk signaling pathways. Results showed that GnT-III gene expression and its catalytic product bisecting GlcNAc structure decreased and phosphorylation of both Smad3 and Erk1/2 was up-regulated in TGF-β1-treated MHCC97-L cells, while GnT-III mRNA expression and bisecting GlcNAc structure increased after blocking the activities of Smad3 and Erk signaling pathways. These findings suggested that GnT-III gene expression is modulated by the growth factor signaling pathways in the EMT model and that GnT-III may be a potential drug target for HCC treatment.
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.|First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi 530021, China.|These authors contributed equally to this article.
authors.forename: Cuiju
authors.initials: C
authors.lastname: Mo
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.|Cancer Research Center, Institute of Biomedical Sciences, Fudan University, Shanghai 200032, China.|These authors contributed equally to this article.
authors.forename: Tianhua
authors.initials: T
authors.lastname: Liu
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Guo
authors.affiliation: First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.affiliation: First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Qin
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.|Cancer Research Center, Institute of Biomedical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Yinkun
authors.initials: Y
authors.lastname: Liu
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; D017351:N-Acetylglucosaminyltransferases; C054599:beta-1,4-mannosyl-glycoprotein beta-1,4-N-acetylglucosaminyltransferase; D048049:Extracellular Signal-Regulated MAP Kinases