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: Binbin Huang, Longe Sun, Jianchun Cao, Yunyun Zhang, Qiong Wu, Junjie Zhang, Yanli Ge, Liu Fu, Zhirong Wang
• Journal: Oncology reports (Oncol Rep) Vol. 29 Issue 6 Pg. 2392-400 (Jun 2013) ISSN: 1791-2431 [Electronic] Greece
• PMID: 23563846 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• CDH1 protein, human
• Cadherins
• RNA, Messenger
• RNA, Small Interfering
• Vimentin
• N-Acetylglucosaminyltransferases
• alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase
• ErbB Receptors
• MMP2 protein, human
• Matrix Metalloproteinase 2
• MMP9 protein, human
• Matrix Metalloproteinase 9

Topics

• Antigens, CD
• Cadherins (metabolism)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Down-Regulation
• ErbB Receptors (metabolism)
• Gene Knockdown Techniques
• Glycosylation
• Humans
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• N-Acetylglucosaminyltransferases (genetics, metabolism)
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Protein Processing, Post-Translational
• RNA, Messenger (genetics, metabolism)
• RNA, Small Interfering (genetics)
• Stomach Neoplasms (pathology)
• Vimentin (metabolism)