The Novel Protein Suppressed in Lung Cancer Down-Regulated in Lung Cancer Tissues Retards Cell Proliferation and Inhibits the Oncokinase Aurora-A

NCU Institutional Repository > 生醫理工學院 > 系統生物與生物資訊研究所 > 期刊論文 > Item 987654321/51088

jsp.display-item.identifier=請使用永久網址來引用或連結此文件: http://ir.lib.ncu.edu.tw/handle/987654321/51088

题名:	The Novel Protein Suppressed in Lung Cancer Down-Regulated in Lung Cancer Tissues Retards Cell Proliferation and Inhibits the Oncokinase Aurora-A
作者:	Yu,CTR;Hsia,JY;Hseih,YC;Su,LJ;Lee,TC;Ku,CF;Chen,KS;Chen,JMM;Wei,TYW;Lee,YCG;Huang,CYF;Wu,YC;Yang,CY;Hsu,SL
贡献者:	系統生物與生物資訊研究所
关键词:	KINASE INHIBITORS;CARCINOMA MODEL;GENE-MUTATIONS;EXPRESSION;SELENOCYSTEINE;EPIDEMIOLOGY;THERAPY;TARGETS;MITOSIS;MATRIX
日期:	2011
上传时间:	2012-03-27 18:21:03 (UTC+8)
出版者:	國立中央大學
摘要:	Introduction: In an attempt to search for genes with abnormal expression in cancers, Suppressed in Lung Cancer (SLAN, also known as KIAA0256) is found underexpressed in human lung cancer tissues by quantitative real-time PCR (Q-RT-PCR). The study set out to characterize SLAN protein and explore its cellular functions. Methods: SLAN or its specific short hairpin RNA, full length or various deletion mutants were overexpressed in 293T or lung cancer cell lines, and cell proliferation, cell cycle, mitosis progression, and spindle configuration were surveyed. Results: SLAN and its deletion mutants are localized to many subcellular locations such as endoplasmic reticulum (ER), nucleus, nucleolus, spindle pole and midbody, suggesting SLAN may function as a multifunctional protein. Overexpression of SLAN per se or its short hairpin RNAs (shRNAs) inhibits or accelerates cell proliferation through prolonging or shortening mitosis. Time-lapse microscopic recording reveals that cells overexpressing exogenous SLAN are arrested in mitosis or cannot undergo cytokinesis. SLAN 2-551 mutants drastically arrest cells in mitosis, where alpha- and gamma-tubulin are disorganized. SLAN employs C-terminal to interact with Aurora-A, a key mitosis regulator and an oncogenic kinase associated with a wide range of human cancers. SLAN negatively regulates the activity of Aurora-A by directly inhibiting kinase activity in vitro or reducing the level of active Aurora-A in cells. SLAN is frequently reduced in lung cancer tissues overexpressing Aurora-A, arguing for the necessity to suppress SLAN during the Aurora-A-associated cancer formation. Conclusions: Taken together, we have identified a novel protein SLAN downregulated in lung caner, having multiple subcellular localization including spindle matrix and midbody, inhibiting cell proliferation and Aurora-A.
關聯:	JOURNAL OF THORACIC ONCOLOGY
显示于类别:	[系統生物與生物資訊研究所] 期刊論文

文件中的档案:

档案	描述	大小	格式	浏览次数
index.html		0Kb	HTML	722	检视/开启

在NCUIR中所有的数据项都受到原著作权保护.

社群 sharing

数据加载中.....