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题名: Wnt/beta-Catenin Signaling Down-regulates N-Acetylglucosaminyltransferase III Expression THE IMPLICATIONS OF TWO MUTUALLY EXCLUSIVE PATHWAYS FOR REGULATION
作者: Xu, Qingsong1, 2;  Akama, Ryota2;  Isaji, Tomoya2;  Lu, Yingying2;  Hashimoto, Hirokazu2;  Kariya, Yoshinobu2;  Fukuda, Tomohiko2;  Du, Yuguang1;  Gu, Jianguo2
刊名: JOURNAL OF BIOLOGICAL CHEMISTRY
发表日期: 2011-02-01
DOI: 10.1074/jbc.M110.182576
卷: 286, 期:6, 页:4310-4318
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology ;  Life Sciences & Biomedicine
类目[WOS]: Biochemistry & Molecular Biology
研究领域[WOS]: Biochemistry & Molecular Biology
英文摘要: In previous studies, we reported that N-acetylglucosaminyl-transferase III (GnT-III) activity and the enzyme product, bisected N-glycans, both were induced in cells cultured under dense conditions in an E-cadherin-dependent manner (Iijima, J., Zhao, Y., Isaji, T., Kameyama, A., Nakaya, S., Wang, X., Ihara, H., Cheng, X., Nakagawa, T., Miyoshi, E., Kondo, A., Narimatsu, H., Taniguchi, N., and Gu, J. (2006) J. Biol. Chem. 281, 13038-13046). Furthermore, we found that alpha-catenin, a component of the E-cadherin-catenin complex, was also required for this induction (Akama, R., Sato, Y., Kariya, Y., Isaji, T., Fukuda, T., Lu, L., Taniguchi, N., Ozawa, M., and Gu, J. (2008) Proteomics 8, 3221-3228). To further explore the molecular mechanism of this regulation, the roles of beta-catenin, an essential molecule in both cadherin-mediated cell adhesion and canonical Wnt signaling, were investigated. Unexpectedly, shRNA knockdown of beta-catenin resulted in a dramatic increase in GnT-III expression and its product, the bisected N-glycans, which was confirmed by RT-PCR and GnT-III activity and by E4-PHA lectin blot analysis. The induction of GnT-III expression increased bisecting GlcNAc residues on beta 1 integrin, which led to down-regulation of integrin-mediated cell adhesion and cell migration. Immunostaining showed that nuclear localization of beta-catenin was greatly suppressed; intriguingly, the knockdown of beta-catenin in the nuclei was more effective than that in cell-cell contacts in the knockdown cells, which was also confirmed by Western blot analysis. Stimulation of the Wnt signaling pathway by the addition of exogenous Wnt3a or BIO, a GSK-3 beta inhibitor, consistently and significantly inhibited GnT-III expression and its products. Conversely, the inhibition of beta-catenin translocation into the nuclei increased GnT-III activation. Taken together, the results of the present study are the first to clearly demonstrate that GnT-III expression may be precisely regulated by the interplay of E-cadherin-catenin complex-mediated cell-cell adhesion and Wnt/beta-catenin signaling, which are both crucial in the process of epithelial-mesenchymal transitions in physiological and pathological conditions.
关键词[WOS]: MEDIATED CELL-ADHESION ;  BETA-PROPELLER DOMAIN ;  E-CADHERIN ;  ALPHA-CATENIN ;  ENDOPLASMIC-RETICULUM ;  PROTEIN GLYCOSYLATION ;  BREAST-CANCER ;  COMPLEX ;  DISEASE ;  METASTASIS
语种: 英语
WOS记录号: WOS:000286975700030
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/142525
Appears in Collections:中国科学院大连化学物理研究所_期刊论文

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作者单位: 1.Chinese Acad Sci, Dalian Inst Chem Phys, Dalian 116023, Peoples R China
2.Tohoku Pharmaceut Univ, Div Regulatory Glycobiol, Inst Mol Biomembrane & Glycobiol, Aoba Ku, Sendai, Miyagi 9818558, Japan

Recommended Citation:
Xu, Qingsong,Akama, Ryota,Isaji, Tomoya,et al. Wnt/beta-Catenin Signaling Down-regulates N-Acetylglucosaminyltransferase III Expression THE IMPLICATIONS OF TWO MUTUALLY EXCLUSIVE PATHWAYS FOR REGULATION[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2011,286(6):4310-4318.
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