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

• Published in: Oncotarget Vol. 8; no. 4; pp. 5909 - 5923
• Main Authors: Wang, Wu-Ping, Sun, Ying, Lu, Qiang, Zhao, Jin-Bo, Wang, Xue-Jiao, Chen, Zhao, Ni, Yun-Feng, Wang, Ju-Zheng, Han, Yong, Zhang, Zhi-Pei, Yan, Xiao-Long, Li, Xiao-Fei
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 24.01.2017
• Subjects: A549 Cells; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Cell Line, Tumor; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Humans; Interleukin-6 - genetics; Interleukin-6 - metabolism; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Neoplasm Metastasis; Proteasome Endopeptidase Complex - genetics; Proteasome Endopeptidase Complex - metabolism; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Research Paper; Signal Transduction; Smad3 Protein - genetics; Smad3 Protein - metabolism; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - metabolism; Up-Regulation; gankyrin; closed circle; NSCLC; metastasis; EMT
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.13947

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.