Oncotarget

Research Papers:

TMEM17 depresses invasion and metastasis in lung cancer cells via ERK signaling pathway

Xiupeng Zhang, Yong Zhang, Yuan Miao, Haijing Zhou, Guiyang Jiang and Enhua Wang _

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Oncotarget. 2017; 8:70685-70694. https://doi.org/10.18632/oncotarget.19977

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Abstract

Xiupeng Zhang1, Yong Zhang2, Yuan Miao1, Haijing Zhou1, Guiyang Jiang1 and Enhua Wang1

1Department of Pathology, College of Basic Medical Sciences and The First Affiliated Hospital, China Medical University, Shenyang, China

2Department of Pathology, Cancer Hospital of China Medical University, Shenyang, China

Correspondence to:

Enhua Wang, email: [email protected]

Keywords: TMEM17, lung cancer, ERK signaling, snail, occludin and Zo-1

Received: January 02, 2017    Accepted: July 18, 2017    Published: August 07, 2017

ABSTRACT

Transmembrane protein 17(TMEM17) is a newly identified protein, its expression pattern and clinicopathological relevance is still unclear. In this study, western blot assay was performed in 20 paired lung cancer samples and found that TMEM17 protein levels were lower in lung cancer tissues than that in the corresponding normal lung tissues (p=0.010). Immunohistochemistry staining in 143 cases lung cancer specimens also showed that TMEM17 expression in lung cancer tissues were significantly lower than adjacent normal lung tissues (35.7% vs 63.2%, p<0.001). And negative TMEM17 expression was significantly associated with poor histological differentiation (p=0.027), advanced TNM stages (p=0.006), positive lymph node metastasis (p=0.002) and poor prognosis (p=0.002). After overexpressing TMEM17, levels of p-ERK and its downstream molecules, p-P90RSK and Snail, were down-regulated, while levels of Occludin and Zo-1 were up-regulated, which result in the inhibition of invasion and migration ability of lung cancer cells. The effects were reversed by the incorporation of specific ERK inhibitor PD98059. In conclusion, loss of TMEM17 correlates with the development of non-small cell lung cancer (NSCLC) and predicts adverse clinical outcome of NSCLC patients. The effect of TMEM17 on inhibiting invasion and migration may attribute to restoring Occludin and Zo-1 expression through inactivating ERK-P90RSK-Snail pathway.


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