Quantitative proteomic analysis of sphere-forming stem-like oral cancer cells.

Quantitative proteomic analysis of sphere-forming stem-like oral cancer cells.
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DOI:
10.1186/scrt386
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发表时间:
2013
影响因子:
7.5
通讯作者:
Hu S
Hu S
中科院分区:
医学2区
文献类型:
--
作者:
Misuno K;Liu X;Feng S;Hu S

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本研究的目的是利用基于质谱的定量蛋白质组学技术,鉴定在口腔癌干细胞样细胞(CSCs)中可能发挥重要功能的靶蛋白。对来自同一舌鳞状细胞癌的高侵袭性UM 1和低侵袭性UM 2口腔癌细胞系进行球体形成测定,以富集CSC。使用串联质量标签和二维液相色谱结合Orbitrap质谱对CSC样和非CSC UM 1细胞进行定量蛋白质组学分析。发现CSC样癌细胞存在于高侵袭性UM 1细胞系中,但不存在于低侵袭性UM 2细胞系中。与非CSC UM 1细胞相比,CSC样UM 1细胞中干细胞标志物SOX 2、OCT 4、SOX 9和CD 44上调,而HIF-1 α和PGK-1下调。定量蛋白质组学分析表明,在细胞周期、代谢、G蛋白信号转导、翻译延伸、发育和RNA剪接途径中的许多蛋白质在两种细胞表型之间存在差异表达。CREB-1结合蛋白(CBP)和磷酸化CREB-1被发现在CSC样UM 1细胞中显著过表达。CSC样细胞可以从高侵袭性的UM 1口腔癌细胞系中富集,但不能从低侵袭性的UM 2口腔癌细胞系中富集。CSC样和非CSC UM 1细胞之间存在显著的蛋白质组学改变。特别是,CBP和磷酸化CREB-1在CSC样UM 1细胞中与非CSC UM 1细胞相比显著上调,表明CREB通路在CSC样细胞中被激活。
The purpose of this study is to identify target proteins that may play important functional roles in oral cancer stem-like cells (CSCs) using mass spectrometry-based quantitative proteomics. Sphere-formation assays were performed on highly invasive UM1 and lowly invasive UM2 oral cancer cell lines, which were derived from the same tongue squamous cell carcinoma, to enrich CSCs. Quantitative proteomic analysis of CSC-like and non-CSC UM1 cells was carried out using tandem mass tagging and two-dimensional liquid chromatography with Orbitrap mass spectrometry. CSC-like cancer cells were found to be present in the highly invasive UM1 cell line but absent in the lowly invasive UM2 cell line. Stem cell markers SOX2, OCT4, SOX9 and CD44 were up-regulated, whereas HIF-1 alpha and PGK-1 were down-regulated in CSC-like UM1 cells versus non-CSC UM1 cells. Quantitative proteomic analysis indicated that many proteins in cell cycle, metabolism, G protein signal transduction, translational elongation, development, and RNA splicing pathways were differentially expressed between the two cell phenotypes. Both CREB-1-binding protein (CBP) and phosphorylated CREB-1 were found to be significantly over-expressed in CSC-like UM1 cells. CSC-like cells can be enriched from the highly invasive UM1 oral cancer cell line but not from the lowly invasive UM2 oral cancer cell line. There are significant proteomic alterations between CSC-like and non-CSC UM1 cells. In particular, CBP and phosphorylated CREB-1 were significantly up-regulated in CSC-like UM1 cells versus non-CSC UM1 cells, suggesting that the CREB pathway is activated in the CSC-like cells.
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发表时间: 2007-01-01
期刊: ONCOGENE
影响因子: 8
作者:
Chen, Y-J;Chang, J. T.;Cheng, A-J
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发表时间: 2011-09-01
期刊: STEM CELLS
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发表时间: 2010-02-08
期刊: PloS one
影响因子: 3.7
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DOI: 10.1158/1078-0432.ccr-07-4404
发表时间: 2008-07-01
影响因子: 11.5
作者:
Chiou, Shih-Hwa;Yu, Cheng-Chia;Lo, Jeng-Fan
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