title: Downregulation of the GnT-V gene inhibits metastasis and invasion of BGC823 gastric cancer cells.
abstract: Metastatic and invasive potential is a barrier to the successful treatment of gastric cancer. N-acetylgluco-saminyltransferase V (GnT-V), a key enzyme catalyzing the formation of 1,6 N-acetylglucosamine (GlcNAc), has been demonstrated to display a distinct function in different types of tumors. The aim of this study was to investigate the role of GnT-V in the invasive potential of BGC823 human gastric cancer cells in vitro and the possible underlying mechanism. GnT-V was downregulated in BGC823 cells by oligo-siRNA transfection. Cell proliferation and invasiveness were assessed by CCK-8 assay, Tunel assay, scratch-wound assay as well as transwell assay. The products of GnT-V, β1-6 branching of asparagine-linked oligosaccharides, were determined by L-PHA lectin blot analysis. The expression of EGFRs, E-cadherin/vimentin and MMP-2/MMP-9 was analyzed both at the mRNA and protein levels. The results showed that downregulation of GnT-V decreased proliferation and the metastatic/invasive potential of BGC823 cells. The expression of EGFRs, E-cadherin/vimentin and MMP-9, molecules related to cancer metastasis and invasion in various tumors, were influenced correspondingly. These findings suggest that downregulation of GnT-V inhibited cell metastasis and invasion of BGC823 cells via EGFR signaling-initiated EMT phenotype and MMP-9 expression. These results provide a novel mechanism to explain the role of GnT-V in cell metastasis and invasion.
authors.affiliation: Department of Gastroenterology of Tongji Hospital, Tongji University School of Medicine, Shanghai, PR China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Huang
authors.forename: Longe
authors.initials: L
authors.lastname: Sun
authors.forename: Jianchun
authors.initials: J
authors.lastname: Cao
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.forename: Junjie
authors.initials: J
authors.lastname: Zhang
authors.forename: Yanli
authors.initials: Y
authors.lastname: Ge
authors.forename: Liu
authors.initials: L
authors.lastname: Fu
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Wang
mesh_terms: D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D066246:ErbB Receptors / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006031:Glycosylation; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D013274:Stomach Neoplasms / Q000473:pathology*; D014746:Vimentin / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014746:Vimentin; D017351:N-Acetylglucosaminyltransferases; C052254:alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase; D066246:ErbB Receptors; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9