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ZNF259 inhibits non-small cell lung cancer cells proliferation and invasion by FAK-AKT signaling

Authors Shan Y, Cao W, Wang T, Jiang G, Zhang Y, Yang X

Received 1 September 2017

Accepted for publication 23 November 2017

Published 14 December 2017 Volume 2017:9 Pages 879—889

DOI https://doi.org/10.2147/CMAR.S150614

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 3

Editor who approved publication: Professor Nakshatri


Yuemei Shan,1,2 Wei Cao,1 Tao Wang,1 Guiyang Jiang,Yong Zhang,4 Xianghong Yang1

1Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, China; 2Department of Applied Technology, Institute of Technology of China Medical University, Shenyang, China; 3Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, China; 4Department of Pathology, Cancer Hospital of China Medical University, Shenyang, China

Background: Zinc finger protein 259 (ZNF259) is known to play essential roles in embryonic development and cell cycle regulation. However, its expression pattern and clinicopathological relevance remain unclear.
Materials and methods:
A total of 114 lung cancer specimens were collected. The ZNF259 expression was measured between the lung cancer tissues and the adjacent normal lung tissues by immunohistochemical staining and Western blotting. Moreover, the correlation of ZNF259 expression with clinicopathological features was analyzed in 114 cases of lung cancer. Additionally, ZNF259 was depleted in the lung cancer cells in order to analyze its effect in the lung cancer.
Results: Immunohistochemical staining of 114 lung cancer specimens revealed significantly lower ZNF259 expression in lung cancer tissues than in adjacent normal lung tissues (53.5% vs 71.4%, P<0.001). In addition, ZNF259 downregulation was significantly associated with larger tumor size (P=0.001), advanced TNM stage (P=0.002), and positive lymph node metastasis (P=0.02). Western blotting of 20 paired lung cancer samples revealed lower ZNF259 protein levels in lung cancer tissues than in those of corresponding normal lung tissues (P=0.0032). Depletion of ZNF259 resulted in enhanced levels of p-FAK and p-AKT, CyclinD1, and MMP2, which in turn increased the proliferation and invasion of lung cancer cells. The effects of ZNF259 depletion were reversed by treatment with specific FAK or AKT inhibitors.
Conclusion: ZNF259 depletion is correlated with the development of non-small cell lung cancer (NSCLC) and serves as a predictor of adverse clinical outcome in NSCLC patients. The inhibitory effect of ZNF259 on proliferation and invasion can be attributed to downregulation of CyclinD1 and MMP2 via inactivation of the FAK-AKT pathway.

Keywords: ZNF259, NSCLC, FAK signaling, AKT signaling, proliferation, invasion

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