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学科主题基础医学
GSK-3 beta-Regulated N-Acetyltransferase 10 Is Involved in Colorectal Cancer Invasion
Zhang, Hong; Hou, Wei; Wang, Hua-Li; Liu, Hai-Jing; Jia, Xin-Ying; Zheng, Xing-Zheng; Zou, Yong-Xin; Li, Xin; Hou, Lin; McNutt, Michael A.; Zhang, Bo
刊名CLINICAL CANCER RESEARCH
2014-09-01
DOI10.1158/1078-0432.CCR-13-3477
20期:17页:4717-4729
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology
研究领域[WOS]Oncology
关键词[WOS]GLYCOGEN-SYNTHASE KINASE-3-BETA ; SURFACE-EXPRESSED NUCLEOLIN ; WNT SIGNALING PATHWAY ; BETA-CATENIN ; CELL-SURFACE ; COLON-CANCER ; TRANSCRIPTIONAL ACTIVATION ; CARCINOMA ; PROTEIN ; CYTOSKELETON
英文摘要

Purpose: NAT10 (N-acetyltransferase 10) is a nucleolar protein, but may show subcellular redistribution in colorectal carcinoma. In this study, we evaluated membranous staining of NAT10 in colorectal carcinoma and its clinical implications, and explored the mechanism of regulation of NAT10 redistribution.

Experimental Design: The expression and subcellular redistribution of NAT10, beta-catenin, E-cadherin, and GSK-3 beta were evaluated by immunohistochemistry in 222 cases of colorectal carcinoma. Regulation of NAT10 and its influence on cell motility were analyzed with inhibitors of GSK-3 beta, transfection of wild-type or kinase-inactivated GSK-3 beta, or expression of various domains of NAT10, and evaluated with immunofluorescence, Western blotting, and Transwell assays.

Results: NAT10 localized mainly in the nucleoli of normal tissues, and was redistributed to the membrane in cancer cells, particularly at the invasive "leading edge" of the tumor. This correlated well with nuclear accumulation of b-catenin (P < 0.001; chi(2) = 68.213). In addition, NAT10 membrane staining reflected the depth of invasion and tendency to metastasize (all P values < 0.001), and was associated with a poorer prognosis (P = 0.023; chi(2) = 5.161). Evaluation of the mechanism involved demonstrated that subcellular redistribution of NAT10 may result from its increased stability and nuclear export, which is brought about by inhibition of GSK-3 beta. Moreover, redistribution of NAT10 induces alteration of cytoskeletal dynamics and increases cancer cell motility.

Conclusion: The subcellular redistribution of NAT10 can be induced by decreases in GSK-3 beta activity. This redistribution increases cancer cell motility, and is, thus, correlated with invasive potential and poorer clinical outcome. This finding suggests that NAT10 may be a useful prognostic marker and potential therapeutic target in colorectal carcinoma. (C) 2014 AACR.

语种英语
WOS记录号WOS:000341835500029
项目编号81171907 ; 81372292 ; 200800010060
资助机构National Natural Science Foundation of China ; Research Fund for the Doctoral Program of Higher Education
引用统计
被引频次:16[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/64362
专题北京大学基础医学院_病理学系
北京大学基础医学院
北京大学精神卫生研究所_精神科
作者单位Peking Univ, Hlth Sci Ctr, Dept Pathol, Sch Basic Med Sci, Beijing 100191, Peoples R China
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GB/T 7714
Zhang, Hong,Hou, Wei,Wang, Hua-Li,et al. GSK-3 beta-Regulated N-Acetyltransferase 10 Is Involved in Colorectal Cancer Invasion[J]. CLINICAL CANCER RESEARCH,2014,20(17):4717-4729.
APA Zhang, Hong.,Hou, Wei.,Wang, Hua-Li.,Liu, Hai-Jing.,Jia, Xin-Ying.,...&Zhang, Bo.(2014).GSK-3 beta-Regulated N-Acetyltransferase 10 Is Involved in Colorectal Cancer Invasion.CLINICAL CANCER RESEARCH,20(17),4717-4729.
MLA Zhang, Hong,et al."GSK-3 beta-Regulated N-Acetyltransferase 10 Is Involved in Colorectal Cancer Invasion".CLINICAL CANCER RESEARCH 20.17(2014):4717-4729.
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