Analysis of EGFR signaling pathway in nasopharyngeal carcinoma cells by quantitative phosphoproteomics.
Analysis of EGFR signaling pathway in nasopharyngeal carcinoma cells by quantitative phosphoproteomics.
复制标题
定量磷酸蛋白质组学分析鼻咽癌细胞EGFR信号通路
DOI：
10.1186/1477-5956-9-35
复制
发表时间：
2011-06-28
期刊：
影响因子：
2
通讯作者：
Xiao ZQ
中科院分区：
文献类型：
--
作者：
Ruan L;Li XH;Wan XX;Yi H;Li C;Li MY;Zhang PF;Zeng GQ;Qu JQ;He QY;Li JH;Chen Y;Chen ZC;Xiao ZQ
表皮生长因子受体（EGFR）在鼻咽癌组织中呈高表达，与鼻咽癌的发生发展有关。然而，EGFR在NPC中的下游信号蛋白尚未在系统水平上完全了解。本研究的目的是鉴定鼻咽癌细胞中EGFR信号通路的新下游蛋白。我们分析了EGFR调控的磷酸化蛋白质组在NPC CNE 2细胞使用2D-DIGE和质谱分析后，磷蛋白富集。结果，在CNE 2中鉴定出33个非冗余磷蛋白，包括5个已知的EGFR调控蛋白和28个新的EGFR调控蛋白，选择性验证了3个差异磷蛋白，并发现2个差异磷蛋白（GSTP 1和GRB 2）与磷酸化EGFR相互作用。生物信息学分析表明，33个蛋白中有32个含有磷酸化修饰位点，17个蛋白为信号蛋白。分析了EGFR调节蛋白之一GST P1与化疗耐药性的关系。结果表明，GST P1可能参与EGF刺激的CNE 2细胞对紫杉醇的耐药性。此外，使用Pathway Studio 5.0软件构建了基于鉴定的EGFR调节的磷蛋白的EGFR信号传导网络，其包括典型的和新的EGFR调节的蛋白，并暗示了这些蛋白的可能的生物学作用。这些结果不仅可以丰富我们对EGFR信号转导的认识，而且对于理解EGFR在NPC发病中的分子机制和寻找治疗NPC的靶点具有重要意义。
The epidermal growth factor receptor (EGFR) is usually overexpressed in nasopharyngeal carcinoma (NPC) and is associated with pathogenesis of NPC. However, the downstream signaling proteins of EGFR in NPC have not yet been completely understood at the system level. The aim of this study was identify novel downstream proteins of EGFR signaling pathway in NPC cells. We analyzed EGFR-regulated phosphoproteome in NPC CNE2 cells using 2D-DIGE and mass spectrometry analysis after phosphoprotein enrichment. As a result, 33 nonredundant phosphoproteins including five known EGFR-regulated proteins and twenty-eight novel EGFR-regulated proteins in CNE2 were identified, three differential phosphoproteins were selectively validated, and two differential phosphoproteins (GSTP1 and GRB2) were showed interacted with phospho-EGFR. Bioinformatics analysis showed that 32 of 33 identified proteins contain phosphorylation modification sites, and 17 identified proteins are signaling proteins. GSTP1, one of the EGFR-regulated proteins, associated with chemoresistance was analyzed. The results showed that GSTP1 could contribute to paclitaxel resistance in EGF-stimulated CNE2 cells. Furthermore, an EGFR signaling network based on the identified EGFR-regulated phosphoproteins were constructed using Pathway Studio 5.0 software, which includes canonical and novel EGFR-regulated proteins and implicates the possible biological roles for those proteins. The data not only can extend our knowledge of canonical EGFR signaling, but also will be useful to understand the molecular mechanisms of EGFR in NPC pathogenesis and search therapeutic targets for NPC.
登录
查看更多内容
影响因子：
46.9
作者：
Blagoev, B;Ong, SE;Mann, M
通讯作者：
Mann, M
影响因子：
6.4
作者：
Xiao, Xia;Wu, Jiangxue;Huang, Wenlin
通讯作者：
Huang, Wenlin
影响因子：
4.7
作者：
PETERS, WHM;WORMSKAMP, NGM;THIES, E
通讯作者：
THIES, E
DOI：
10.1002/hed.10307
发表时间：
2003-10-01
影响因子：
2.9
作者：
Ma, BBT;Poon, TCW;Chan, ATC
通讯作者：
Chan, ATC
影响因子：
3.4
作者：
Friedman, DB;Hill, S;Caprioli, RM
通讯作者：
Caprioli, RM