Overexpression of Human Papillomavirus Type 16 Oncoproteins Enhances Epithelial-Mesenchymal Transition via STAT3 Signaling Pathway in Non-Small Cell Lung Cancer Cells.
Overexpression of Human Papillomavirus Type 16 Oncoproteins Enhances Epithelial-Mesenchymal Transition via STAT3 Signaling Pathway in Non-Small Cell Lung Cancer Cells.
复制标题
人乳头瘤病毒 16 型癌蛋白的过度表达通过 STAT3 信号通路增强非小细胞肺癌细胞的上皮-间质转化
DOI：
10.3727/096504016x14813880882288
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发表时间：
2017-05-24
影响因子：
3.1
通讯作者：
Tang X
中科院分区：
文献类型：
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作者：
Zhang W;Wu X;Hu L;Ma Y;Xiu Z;Huang B;Feng Y;Tang X
人乳头瘤病毒（HPV）感染可能与非小细胞肺癌（NSCLC）的发生和进展有关。然而，HPV-16癌蛋白在非小细胞肺癌发生发展中的作用尚不完全清楚。上皮间充质转化（Epithelial-mesenchymal transition， EMT）在非小细胞肺癌的发生发展中起着关键作用，是侵袭转移的关键步骤。在这里，我们探讨了HPV-16癌蛋白对EMT的影响及其潜在机制。用EGFP-N1-HPV-16 E6或E7质粒瞬时转染NSCLC细胞株A549和NCI-H460。采用Real-time PCR和Western blot分析EMT标志物的表达情况。利用蛋白质微阵列对相关信号通路进行筛选。我们的研究结果表明，在NSCLC细胞中过表达HPV-16 E6和E7癌蛋白可显著促进EMT样形态学改变，下调EMT上皮标记物（E-cadherin和ZO-1） mRNA和蛋白水平，上调EMT间质标记物（N-cadherin和vimentin）和转录因子（ZEB-1和Snail-1） mRNA和蛋白水平。此外，hpv - 16e6癌蛋白促进STAT3的激活。此外，WP1066是一种特异性的信号换能器和转录3激活因子（STAT3）抑制剂，可以逆转HPV-16 E6对转染NSCLC细胞中ZO-1、vimentin和ZEB-1表达的影响。综上所述，我们的研究结果表明，HPV-16 E6和E7癌蛋白的过表达增强了EMT， STAT3信号通路可能参与了HPV-16 E6诱导的NSCLC细胞EMT。
The human papillomavirus (HPV) infection may be associated with the development and progression of non-small cell lung cancer (NSCLC). However, the role of HPV-16 oncoproteins in the development and progression of NSCLC is not completely clear. Epithelial–mesenchymal transition (EMT), a crucial step for invasion and metastasis, plays a key role in the development and progression of NSCLC. Here we explored the effect of HPV-16 oncoproteins on EMT and the underlying mechanisms. NSCLC cell lines, A549 and NCI-H460, were transiently transfected with the EGFP-N1-HPV-16 E6 or E7 plasmid. Real-time PCR and Western blot analysis were performed to analyze the expression of EMT markers. A protein microarray was used to screen the involved signaling pathway. Our results showed that overexpression of HPV-16 E6 and E7 oncoproteins in NSCLC cells significantly promoted EMT-like morphologic changes, downregulated the mRNA and protein levels of EMT epithelial markers (E-cadherin and ZO-1), and upregulated the mRNA and protein levels of EMT mesenchymal markers (N-cadherin and vimentin) and transcription factors (ZEB-1 and Snail-1). Furthermore, the HPV-16 E6 oncoprotein promoted STAT3 activation. Moreover, WP1066, a specific signal transducer and activator of transcription 3 (STAT3) inhibitor, reversed the effect of HPV-16 E6 on the expression of ZO-1, vimentin, and ZEB-1 in transfected NSCLC cells. Taken together, our results suggest that overexpression of HPV-16 E6 and E7 oncoproteins enhances EMT, and the STAT3 signaling pathway may be involved in HPV-16 E6-induced EMT in NSCLC cells.