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Elevated O-GlcNAcylation promotes gastric cancer cells proliferation by modulating cell cycle related proteins and ERK 1/2 signaling
O-GlcNAc transferase (OGT) is the only enzyme in mammals that catalyzes the attachment of β-D-N-acetylglucosamine (GlcNAc) to serine or threonine residues of target proteins. Hyper-O-GlcNAcylation is becoming increasingly realized as a general feature of cancer and contributes to rapid proliferation...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5308659/ https://www.ncbi.nlm.nih.gov/pubmed/27542217 http://dx.doi.org/10.18632/oncotarget.11359 |
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author | Jiang, Mingzuo Qiu, Zhaoyan Zhang, Song Fan, Xing Cai, Xiqiang Xu, Bing Li, Xiaowei Zhou, Jinfeng Zhang, Xiangyuan Chu, Yi Wang, Weijie Liang, Jie Horvath, Tamas Yang, Xiaoyong Wu, Kaichun Nie, Yongzhan Fan, Daiming |
author_facet | Jiang, Mingzuo Qiu, Zhaoyan Zhang, Song Fan, Xing Cai, Xiqiang Xu, Bing Li, Xiaowei Zhou, Jinfeng Zhang, Xiangyuan Chu, Yi Wang, Weijie Liang, Jie Horvath, Tamas Yang, Xiaoyong Wu, Kaichun Nie, Yongzhan Fan, Daiming |
author_sort | Jiang, Mingzuo |
collection | PubMed |
description | O-GlcNAc transferase (OGT) is the only enzyme in mammals that catalyzes the attachment of β-D-N-acetylglucosamine (GlcNAc) to serine or threonine residues of target proteins. Hyper-O-GlcNAcylation is becoming increasingly realized as a general feature of cancer and contributes to rapid proliferation of cancer cells. In this study, we demonstrated that O-GlcNAc and OGT levels were increased in all six gastric cancer (GC) cell lines as compared with immortal gastric epithelial cells. Downregulation of the O-GlcNAcylation level by silencing OGT inhibited cell viability and growth rate via the cdk-2, cyclin D1 and ERK 1/2 pathways. In vivo xenograft assays also demonstrated that the hyper-O-GlcNAc level markedly promoted the proliferation of tumors. Moreover, compared with noncancerous tissues, the O-GlcNAcylation level was increased in cancerous tissues. GC patients with higher levels of O-GlcNAcylation exhibited large tumor sizes (≥5 cm), deep tumor invasion (T3 and T4), high AJCC stages (stage III and IV), more lymph node metastases and lower overall survival. Notably, the phosphorylation level of ERK 1/2 was increased progressively with the increase of O-GlcNAcylation in both SGC 7901 and AGS cells. Consistently, human GC tissue arrays also revealed that ERK 1/2 signaling was positively correlated to O-GlcNAcylation (r = 0.348; P = 0.015). Taken together, here we reported that hyper-O-GlcNAcylation significantly promotes GC cells proliferation by modulating cell cycle related proteins and ERK 1/2 signaling, suggesting that inhibition of OGT may be a potential novel therapeutic target of GC. |
format | Online Article Text |
id | pubmed-5308659 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53086592017-03-09 Elevated O-GlcNAcylation promotes gastric cancer cells proliferation by modulating cell cycle related proteins and ERK 1/2 signaling Jiang, Mingzuo Qiu, Zhaoyan Zhang, Song Fan, Xing Cai, Xiqiang Xu, Bing Li, Xiaowei Zhou, Jinfeng Zhang, Xiangyuan Chu, Yi Wang, Weijie Liang, Jie Horvath, Tamas Yang, Xiaoyong Wu, Kaichun Nie, Yongzhan Fan, Daiming Oncotarget Research Paper O-GlcNAc transferase (OGT) is the only enzyme in mammals that catalyzes the attachment of β-D-N-acetylglucosamine (GlcNAc) to serine or threonine residues of target proteins. Hyper-O-GlcNAcylation is becoming increasingly realized as a general feature of cancer and contributes to rapid proliferation of cancer cells. In this study, we demonstrated that O-GlcNAc and OGT levels were increased in all six gastric cancer (GC) cell lines as compared with immortal gastric epithelial cells. Downregulation of the O-GlcNAcylation level by silencing OGT inhibited cell viability and growth rate via the cdk-2, cyclin D1 and ERK 1/2 pathways. In vivo xenograft assays also demonstrated that the hyper-O-GlcNAc level markedly promoted the proliferation of tumors. Moreover, compared with noncancerous tissues, the O-GlcNAcylation level was increased in cancerous tissues. GC patients with higher levels of O-GlcNAcylation exhibited large tumor sizes (≥5 cm), deep tumor invasion (T3 and T4), high AJCC stages (stage III and IV), more lymph node metastases and lower overall survival. Notably, the phosphorylation level of ERK 1/2 was increased progressively with the increase of O-GlcNAcylation in both SGC 7901 and AGS cells. Consistently, human GC tissue arrays also revealed that ERK 1/2 signaling was positively correlated to O-GlcNAcylation (r = 0.348; P = 0.015). Taken together, here we reported that hyper-O-GlcNAcylation significantly promotes GC cells proliferation by modulating cell cycle related proteins and ERK 1/2 signaling, suggesting that inhibition of OGT may be a potential novel therapeutic target of GC. Impact Journals LLC 2016-08-17 /pmc/articles/PMC5308659/ /pubmed/27542217 http://dx.doi.org/10.18632/oncotarget.11359 Text en Copyright: © 2016 Jiang et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Jiang, Mingzuo Qiu, Zhaoyan Zhang, Song Fan, Xing Cai, Xiqiang Xu, Bing Li, Xiaowei Zhou, Jinfeng Zhang, Xiangyuan Chu, Yi Wang, Weijie Liang, Jie Horvath, Tamas Yang, Xiaoyong Wu, Kaichun Nie, Yongzhan Fan, Daiming Elevated O-GlcNAcylation promotes gastric cancer cells proliferation by modulating cell cycle related proteins and ERK 1/2 signaling |
title | Elevated O-GlcNAcylation promotes gastric cancer cells proliferation by modulating cell cycle related proteins and ERK 1/2 signaling |
title_full | Elevated O-GlcNAcylation promotes gastric cancer cells proliferation by modulating cell cycle related proteins and ERK 1/2 signaling |
title_fullStr | Elevated O-GlcNAcylation promotes gastric cancer cells proliferation by modulating cell cycle related proteins and ERK 1/2 signaling |
title_full_unstemmed | Elevated O-GlcNAcylation promotes gastric cancer cells proliferation by modulating cell cycle related proteins and ERK 1/2 signaling |
title_short | Elevated O-GlcNAcylation promotes gastric cancer cells proliferation by modulating cell cycle related proteins and ERK 1/2 signaling |
title_sort | elevated o-glcnacylation promotes gastric cancer cells proliferation by modulating cell cycle related proteins and erk 1/2 signaling |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5308659/ https://www.ncbi.nlm.nih.gov/pubmed/27542217 http://dx.doi.org/10.18632/oncotarget.11359 |
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