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Potential role of O‐GlcNAcylation and involvement of PI3K/Akt1 pathway in the expression of oncogenic phenotypes of gastric cancer cells in vitro
Author(s) -
Zhang Nuobei,
Chen Xin
Publication year - 2015
Publication title -
biotechnology and applied biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 70
eISSN - 1470-8744
pISSN - 0885-4513
DOI - 10.1002/bab.1441
Subject(s) - akt1 , downregulation and upregulation , pi3k/akt/mtor pathway , protein kinase b , cell growth , small hairpin rna , cancer research , phosphorylation , biology , microbiology and biotechnology , cancer cell , chemistry , signal transduction , cancer , biochemistry , apoptosis , gene knockdown , gene , genetics
O‐GlcNAcylation is a monosaccharide modification by a residue of N‐acetylglucosamine (GlcNAc) attached to serine or threonine moieties on nuclear and cytoplasmic proteins. O‐GlcNAcylation is dynamically regulated by O‐GlcNAc transferase (OGT) and O‐GlcNAcase (OGA). Increasing evidence suggests that O‐GlcNAcylation is involved in a variety of human cancers. However, the exact role of O‐GlcNAcylation in tumor progression remains unclear. Here, we show that O‐GlcNAcylation accelerates oncogenic phenotypes of gastric cancer. First, cell models with increased or decreased O‐GlcNAcylation were constructed by OGT overexpression, downregulation of OGA activity with specific inhibitor Thiamet‐G, or silence of OGT. MTT assays indicated that O‐GlcNAcylation increased proliferation of gastric cancer cells. Soft agar assay and Transwell assays showed that O‐GlcNAcylation significantly enhanced cellular colony formation, migration, and invasion in vitro . Akt1 activity was stimulated by upregulation of phosphorylation at Ser473 mediated by elevated O‐GlcNAcylation. The enhanced cell invasion by Thiamet‐G treatment was suppressed by PI3K inhibitor LY294002. Although the cell invasion induced by Thiamet‐G was reduced by Akt1 shRNA, it was still higher in comparison with that to the control (cells with Akt1 shRNA alone). And Akt1 overexpression promoted Thiamet‐G‐induced cell invasion. These results suggested that O‐GlcNAcylation enhanced oncogenic phenotypes possibly partially involving PI3K/Akt signaling pathway.