
@Article{096504016X14813880882288,
AUTHOR = {Wenzhang Zhang, Xin Wu, Liang Hu, Yuefan Ma, Zihan Xiu, Bingyu Huang, Yun Feng, Xudong Tang},
TITLE = {Overexpression of Human Papillomavirus Type 16 Oncoproteins Enhances  Epithelial–Mesenchymal Transition via STAT3 Signaling Pathway  in Non-Small Cell Lung Cancer Cells},
JOURNAL = {Oncology Research},
VOLUME = {25},
YEAR = {2017},
NUMBER = {5},
PAGES = {843--852},
URL = {http://www.techscience.com/or/v25n5/56866},
ISSN = {1555-3906},
ABSTRACT = {The human papillomavirus (HPV) infection may be associated with the development and progression of nonsmall 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.},
DOI = {10.3727/096504016X14813880882288}
}



