Quantitative iTRAQ LC-MS/MS Proteomics Reveals Transcription Factor Crosstalk and Regulatory Networks in Hypopharyngeal Squamous Cell Carcinoma.

Quantitative iTRAQ LC-MS/MS Proteomics Reveals Transcription Factor Crosstalk and Regulatory Networks in Hypopharyngeal Squamous Cell Carcinoma.
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定量 iTRAQ LC-MS/MS 蛋白质组学揭示下咽鳞状细胞癌中的转录因子串扰和调节网络

DOI:
10.7150/jca.9207
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发表时间:
2014
期刊:
影响因子:
3.9
通讯作者:
Zhang X
Zhang X
中科院分区:
医学3区
文献类型:
--
作者:
Zhu G;Cai G;Liu Y;Tan H;Yu C;Huang M;Wei M;Li S;Cui X;Huang D;Tian Y;Zhang X

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到目前为止,下咽鳞状细胞癌(HPSCC)还没有开发出有效的治疗方法,由于其诊断较晚和侵袭性,这种疾病的五年生存率约为31%。尽管最近诊断方法有所改进,但没有有效的措施来预防或早期发现HPSCC。本研究的目的是确定分子生物标志物和网络,可以促进快速识别可以从个体化治疗中受益的HPSCC患者。采用同位素相对和绝对定量标记(iTRAQ)技术,结合二维液相色谱-串联质谱技术,对HPSCC 3种疾病分期的差异表达蛋白进行定量鉴定。通过文献检索和蛋白质印迹分析评价iTRAQ结果。例如,FUBP 1,412种具有显著改变的表达谱的蛋白之一,被证实在新鲜的HPSCC组织中具有升高的表达。整合素介导的细胞基质粘附和肌动蛋白介导的细胞骨架重塑是与HPSCC肿瘤发生和转移过程最相关的细胞事件。转录调控网络的构建导致了HPSCC的肿瘤发展和淋巴结转移的关键转录调控因子的鉴定,包括Sp1,c-Myc和p53。此外,本研究还提示Sp1、c-Myc和p53之间的相互作用可能在HPSCC的发生和转移中起重要作用。
To date, no effective therapeutic treatments have been developed for hypopharyngeal squamous cell carcinoma (HPSCC), a disease that has a five-year survival rate of approximately 31% because of its late diagnosis and aggressive nature. Despite recent improvements in diagnostic methods, there are no effective measures to prevent or detect HPSCC in an early stage. The goal of the current study was to identify molecular biomarkers and networks that can facilitate the speedy identification of HPSCC patients who could benefit from individualized treatment. Isobaric tags for relative and absolute quantification (iTRAQ) labeling was employed with two-dimensional liquid chromatography-tandem mass spectrometry to identify quantitatively the differentially expressed proteins among three types of HPSCC disease stages. The iTRAQ results were evaluated by literature searches and western blot analysis. For example, FUBP1, one of 412 proteins with significantly altered expression profiles, was confirmed to have elevated expression in fresh HPSCC tissues. Integrin-mediated cell matrix adhesion and actin filament-inducing cytoskeleton remodeling were the cellular events that were the most relevant to HPSCC tumorigenesis and the metastatic process. The construction of transcriptional regulation networks led to the identification of key transcriptional regulators of tumor development and lymph node metastasis of HPSCC, including Sp1, c-Myc and p53. Additionally, our study indicated that the interactions among Sp1, c-Myc and p53 may play vital roles in the carcinogenesis and metastasis of HPSCC.
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