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

Abstract

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.

• Authors: Yuemei Shan, Wei Cao, Tao Wang, Guiyang Jiang, Yong Zhang, Xianghong Yang
• Journal: Cancer management and research (Cancer Manag Res) Vol. 9 Pg. 879-889 ( 2017) ISSN: 1179-1322 [Print] New Zealand
• PMID: 29276408 (Publication Type: Journal Article)