Oncotarget

Research Papers:

Gankyrin promotes epithelial-mesenchymal transition and metastasis in NSCLC through forming a closed circle with IL-6/ STAT3 and TGF-β/SMAD3 signaling pathway

Wu-ping Wang, Ying Sun, Qiang Lu, Jin-bo Zhao, Xue-jiao Wang, Zhao Chen, Yun-feng Ni, Ju-zheng Wang, Yong Han, Zhi-pei Zhang, Xiao-long Yan and Xiao-fei Li _

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Oncotarget. 2017; 8:5909-5923. https://doi.org/10.18632/oncotarget.13947

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Abstract

Wu-ping Wang1,*, Ying Sun1,*, Qiang Lu1,*, Jin-bo Zhao1, Xue-jiao Wang1, Zhao Chen1, Yun-feng Ni1, Ju-zheng Wang1, Yong Han1, Zhi-pei Zhang1, Xiao-long Yan1, Xiao-fei Li1

1Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi’an, 710038, China

*These authors contributed equally to this work

Correspondence to:

Zhi-pei Zhang, email: zzpzyy@fmmu.edu.cn

Xiao-long Yan, email: yanxiaolong@fmmu.edu.cn

Xiao-fei Li, email: lxfchest@fmmu.edu.cn

Keywords: NSCLC, gankyrin, EMT, metastasis, closed circle

Received: September 02, 2016     Accepted: December 08, 2016     Published: December 15, 2016

ABSTRACT

Our previous research showed that Gankyrin was overexpressed in NSCLC and significantly associated with clinicopathologic features and poor prognosis. In this study, we will explore potential effect of Gankyrin on EMT and metastasis in NSCLC. The ectopic higher expression of Gankyrin markedly increased the migration and invasion in NSCLC cells. In contrast, silencing Gankyrin inhibit this aggressive behavior in NSCLC cells. Further study demonstrated that overexpression of Gankyrin could decrease E-cadherin expression and increase expression of Vimentin and Twist1 at mRNA and protein levels. These data indicated that Gankyrin could facilitate occurrence and development of EMT. Also IHC analysis showed that Gankyrin expression was negatively correlated with E-cadherin expression, while positively correlated with Vimentin and Twist1 expression in NSCLC tissues. The mechanism study finally suggested that the Gankyrin-driven EMT was partially due to IL-6/p-STAT3 and TGF-β/p-SMAD3 pathways activation. Taken together, our data provided a novel mechanism of Gankyrin promoting EMT and metastasis in NSCLC through forming a closed circle with IL-6/p-STAT3 and TGF-β/p-SMAD3 signaling pathway.


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