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学科主题: 基础医学
题名:
GSK-3 beta-Regulated N-Acetyltransferase 10 Is Involved in Colorectal Cancer Invasion
作者: 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
发表日期: 2014-09-01
DOI: 10.1158/1078-0432.CCR-13-3477
卷: 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
所属项目编号: 81171907 ; 81372292 ; 200800010060
项目资助者: National Natural Science Foundation of China ; Research Fund for the Doctoral Program of Higher Education
WOS记录号: WOS:000341835500029
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/64362
Appears in Collections:基础医学院_病理学系_期刊论文

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作者单位: Peking Univ, Hlth Sci Ctr, Dept Pathol, Sch Basic Med Sci, Beijing 100191, Peoples R China

Recommended Citation:
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.
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