Oncotarget

Research Papers:

The coiled-coil domain of oncogene RASSF 7 inhibits hippo signaling and promotes non-small cell lung cancer

Xiaoying Zheng, Qianze Dong, Xiupeng Zhang, Qiang Han, Xu Han, Yong Han, Jingjing Wu, Xuezhu Rong and Enhua Wang _

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Oncotarget. 2017; 8:78734-78748. https://doi.org/10.18632/oncotarget.20223

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Abstract

Xiaoying Zheng1,2, Qianze Dong1, Xiupeng Zhang1, Qiang Han1, Xu Han1, Yong Han1, Jingjing Wu1, Xuezhu Rong1 and Enhua Wang1

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

2Department of Electron Microscopy, Basic Medical College, Chengde Medical College, Chengde, China

Correspondence to:

Enhua Wang, email: wangeh@hotmail.com

Keywords: RASSF7, hippo signaling pathway, non-small cell lung cancer, proliferation, migration

Received: March 26, 2017    Accepted: July 12, 2017    Published: August 12, 2017

ABSTRACT

Lung cancer is the leading cause of cancer-related deaths worldwide, and despite recent improvements in treatment patient prognosis remains dismal. In this study, we examined the role of N-terminal Ras-association domain family 7 (RASSF7) in human non-small cell lung cancer (NSCLC). We found that RASSF7 was overexpressed NSCLC tissues, which correlated with advanced TNM stage, positive lymph node metastasis, and poor prognosis. This RASSF7 overexpression promoted lung cancer cell proliferation, migration, and invasion. We also found that RASSF7 interacted with mammalian Ste20-like kinase 1(MST1) through its C-terminal coiled-coil domain to inhibit MST1 phosphorylation as well as the phosphorylation of large tumor suppressor kinase 1(LATS1) and yes-associated protein (YAP), while promoting the nuclear translocation of YAP. In addition, RASSF7 overexpression inhibited the Hippo signaling pathway both in vitro and vivo and promoted the expression of proteins associated with proliferation and invasion, such as connective tissue growth factor. These results suggest that targeting RASSF7 could be exploited for therapeutic benefit in the treatment of NSCLC.


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