Oncotarget

Research Papers:

Identification of a novel YAP–14-3-3ζ negative feedback loop in gastric cancer

Bin Zhang, Aihua Gong, Hui Shi, Qingli Bie, Zhaofeng Liang, Peipei Wu, Fei Mao, Hui Qian and Wenrong Xu _

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Oncotarget. 2017; 8:71894-71910. https://doi.org/10.18632/oncotarget.18011

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Abstract

Bin Zhang1, Aihua Gong1, Hui Shi1, Qingli Bie1, Zhaofeng Liang1, Peipei Wu1, Fei Mao1, Hui Qian1 and Wenrong Xu1,2

1Key Laboratory of Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, P.R. China

2The Affiliated Hospital, Jiangsu University, Zhenjiang, Jiangsu, P.R. China

Correspondence to:

Wenrong Xu email: [email protected]

Hui Qian email: [email protected]

Keywords: YAP, 14-3-3ζ, MDM2, hippo, gastric cancer

Received: April 04, 2017     Accepted: May 09, 2017     Published: May 19, 2017

ABSTRACT

Growing evidence indicates that 14-3-3ζ and yes-associated protein (YAP) substantially promote tumorigenesis and tumor development. However, the regulatory mechanism underlying these two proteins remains unknown. Herein, we report a new regulatory role of 14-3-3ζ in the phosphorylation of YAP and the feedback inhibition of 14-3-3ζ by YAP. YAP and 14-3-3ζ expression exhibited a negative correlation in gastric cancer (GC) tissues. Moreover, patients with higher YAP and lower 14-3-3ζ expression had poor prognoses. Studies have revealed that 14-3-3ζ promotes cytoplasmic retention and suppresses the transcriptional activity of YAP by inducing its phosphorylation. Furthermore, we observed that the overexpression of YAP significantly reduced the expression of 14-3-3ζ by inducing its ubiquitination. YAP, 14-3-3ζ, and mouse double minute 2 homolog (MDM2) were colocalized, and the knockdown of MDM2 by siRNA attenuated the YAP-induced decrease of 14-3-3ζ. The binding of 14-3-3ζ and MDM2 was also restrained when the expression of YAP was interfered. Our results indicated the presence of a 14-3-3ζ–YAP negative regulatory feedback loop, which has a crucial role in cell proliferation and survival and is a potential target for the clinical treatment of GC.


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