Oncotarget

Research Papers:

This article has been corrected. Correction in: Oncotarget. 2019; 10:6285-6285.

Protein 4.1N acts as a potential tumor suppressor linking PP1 to JNK-c-Jun pathway regulation in NSCLC

Zi Wang, Bianyin Ma, Hui Li, Xiaojuan Xiao, Weihua Zhou, Feng Liu, Bin Zhang, Min Zhu, Qin Yang, Yayue Zeng, Yang Sun, Shuming Sun, Yanpeng Wang, Yibin Zhang, Haibo Weng, Lixiang Chen, Mao Ye, Xiuli An and Jing Liu _

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Oncotarget. 2016; 7:509-523. https://doi.org/10.18632/oncotarget.6312

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Abstract

Zi Wang1,2,*, Bianyin Ma1,*, Hui Li1,*, Xiaojuan Xiao1,*, Weihua Zhou1,3, Feng Liu2, Bin Zhang4, Min Zhu1, Qin Yang1, Yayue Zeng1, Yang Sun5, Shuming Sun1, Yanpeng Wang1, Yibin Zhang1, Haibo Weng6, Lixiang Chen6, Mao Ye5, Xiuli An6,7, Jing Liu1

1The State Key Laboratory of Medical Genetics and School of Life Sciences, Central South University, Changsha, China

2Department of Medicine, University of California, Irvine, CA, USA

3Department of Biochemistry, College of Medicine, Jishou University, Jishou, China

4Department of Histology and Embryology, Xiangya School of Medicine, Central South University, Changsha, China

5Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, China

6College of Life Sciences, Zhengzhou University, Zhengzhou, China

7Laboratory of Membrane Biology, New York Blood Center, New York, NY, USA

*These authors contributed equally to this work

Correspondence to:

Jing Liu, e-mail: [email protected] and [email protected]

Xiuli An, e-mail: [email protected]

Mao Ye, e-mail: [email protected]

Keywords: protein 4.1N, non-small cell lung cancer, tumor suppressor, PP1, JNK/c-Jun pathway

Received: October 29, 2015     Accepted: November 02, 2015     Published: November 13, 2015

ABSTRACT

Protein 4.1N is a member of protein 4.1 family and has been recognized as a potential tumor suppressor in solid tumors. Here, we aimed to investigate the role and mechanisms of 4.1N in non-small cell lung cancer (NSCLC). We confirmed that the expression level of 4.1N was inversely correlated with the metastatic properties of NSCLC cell lines and histological grade of clinical NSCLC tissues. Specific knockdown of 4.1N promoted tumor cell proliferation, migration and adhesion in vitro, and tumor growth and metastasis in mouse xenograft models. Furthermore, we identified PP1 as a novel 4.1N-interacting molecule, and the FERM domain of 4.1N mediated the interaction between 4.1N and PP1. Further, ectopic expression of 4.1N could inactivate JNK-c-Jun signaling pathway through enhancing PP1 activity and interaction between PP1 and p-JNK. Correspondingly, expression of potential downstream metastasis targets (ezrin and MMP9) and cell cycle targets (p53, p21 and p19) of JNK-c-Jun pathway were also regulated by 4.1N. Our data suggest that down-regulation of 4.1N expression is a critical step for NSCLC development and that repression of JNK-c-Jun signaling through PP1 is one of the key anti-tumor mechanisms of 4.1N.


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