Epithelial-mesenchymal transition in cervical cancer: Correlation with tumor progression, epidermal growth factor receptor overexpression, and snail up-regulation
Epithelial-mesenchymal transition in cervical cancer: Correlation with tumor progression, epidermal growth factor receptor overexpression, and snail up-regulation
复制标题
DOI：
10.1158/1078-0432.ccr-08-0234
复制
发表时间：
2008-08-01
影响因子：
11.5
通讯作者：
Shen, Meng-Ru
中科院分区：
文献类型：
--
作者：
Lee, Mei-Yi;Chou, Cheng-Yang;Shen, Meng-Ru
目的：原发性癌细胞获得上皮-间质转化（EMT）与上皮完整性破坏、局部侵袭和最终转移有关。关于EMT在宫颈癌中的存在及其作用，目前所知甚少。本研究旨在探讨EMT在宫颈鳞状细胞癌中的调控作用。实验设计：我们研究了EMT在手术标本中的分子事件，这些标本反映了宫颈癌的进展。以两株宫颈癌细胞系和正常宫颈上皮原代培养细胞为实验材料，研究了EMT的调控机制。结果：慢性表皮生长因子（EGF）处理可诱导细胞形态伸长，增加细胞散射，增强细胞侵袭能力。EGF处理可下调宫颈癌细胞中E-cadherin，上调vimentin。这些特征与EMT EGF受体（EGFR）信号通路的形态变化、分子事件和功能意义相一致，使糖原合成酶激酶-3 β失活，导致蜗牛细胞核积累上调，进而导致EMT程序。α (5) β(1)整合素信号和细胞外基质纤维连接蛋白可调节egf诱导的EMT。重要的是，手术标本的免疫荧光染色表明，宫颈癌的进展伴随着EGFR过表达，与E-cadherin减少和vimentin增加平行。在肿瘤组织中，蜗牛基因的上调和核积累与EMT程序有关。结论：EGF与α (5) β(1)整合素信号协同，通过上调Snail介导宫颈癌细胞EMT。阻断EGFR活性或表达可能为治疗宫颈癌进展提供一个潜在的靶点。
Purpose: Acquisition of epithelial-mesenchymal transition (EMT) by primary carcinoma cells is associated with disrupted epithelial integrity, local invasion, and ultimately metastasis. Little is known about the existence and function of EMT in cervical cancer. This study aims to investigate the regulation of EMT in cervical squamous cell carcinoma.Experimental Design: We investigated the molecular events of EMT in surgical specimens, which present the progression of cervical carcinoma. Two cervical cancer cell lines and the primary culture of normal cervical epithelia were used to study the regulatory mechanisms of EMT.Results: The chronic epidermal growth factor (EGF) treatment induces the elongation of cell shape, increases cell scattering, and enhances cell invasion. EGF treatment down-regulates E-cadherin and up-regulates vimentin in cervical cancer cells. These characteristics are consistent with the morphologic changes, molecular events, and functional significance of EMT EGF receptor (EGFR) signaling inactivates glycogen synthase kinase-3 beta, which results in the nuclear accumulation of up-regulated Snail and then leads to EMT program. alpha(5)beta(1) integrin signaling and extracellular matrix fibronectin can modulate EGF-induced EMT Importantly, the immunofluorescent stainings of surgical specimens indicate that cervical carcinoma progression is accompanied by EGFR overexpression, which is in parallel with decreased E-cadherin and increased vimentin. Up-regulation and nuclear accumulation of Snail correlate with EMT program in tumor tissues.Conclusion: EGF cooperates with alpha(5)beta(1) integrin signaling to induce EMT in cervical cancer cells via up-regulated Snail. Blockade of EGFR activity or expression may provide a potential target for the treatment of cervical cancer progression.