Effects and related mechanisms of serotonin on malignant biological behavior of hepatocellular carcinoma via regulation of Yap

Sushun Liu; Runchen Miao; Mimi Zhai; Qing Pang; Yan Deng; Sinan Liu; Kai Qu; Chang Liu; Jingyao Zhang

doi:10.18632/oncotarget.17658

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Research Papers:

Effects and related mechanisms of serotonin on malignant biological behavior of hepatocellular carcinoma via regulation of Yap

Sushun Liu, Runchen Miao, Mimi Zhai, Qing Pang, Yan Deng, Sinan Liu, Kai Qu, Chang Liu and Jingyao Zhang _

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Oncotarget. 2017; 8:47412-47424. https://doi.org/10.18632/oncotarget.17658

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Abstract

Sushun Liu1,2, Runchen Miao1, Mimi Zhai1, Qing Pang1, Yan Deng1, Sinan Liu1, Kai Qu1, Chang Liu1,3 and Jingyao Zhang1,3

1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

2Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, China

3Department of SICU, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

Correspondence to:

Jingyao Zhang, email: [email protected]

Chang Liu, email: [email protected]

Keywords: 5-HT, Yap, 5-HT_2BR, ERK, hepatocellular carcinoma

Received: February 15, 2017 Accepted: April 17, 2017 Published: May 07, 2017

ABSTRACT

5-hydroxytryptamine (5-HT, serotonin) and Yes-associated protein (Yap), which act as a mitogen and an oncogene, respectively, play an important role in tumors. Here, we investigated whether 5-HT could affect the hepatocarcinogenic process via promoting the activation and expression of Yap, as well as the possible underlying molecular mechanisms. We found that 5-HT promoted hepatoma cell proliferation, invasion and metastasis via regulating Yap expression in vitro and in vivo, and Yap knockdown had opposite effects. Furthermore, 5-HT activated 5-HT_2BR to promote Yap expression via upregulating the pERK level. Inhibitors of 5-HT_2BR and ERK attenuated the overexpression of Yap and promotional effects of 5-HT in vitro and in vivo. As a result, 5-HT affected the malignant biological behavior of hepatoma cells via the 5-HT-5-HT_2BR-pERK-Yap axis. Therefore, 5-HT and Yap may be prognostic predictors and potential therapeutic targets for HCC patients in the future.

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Research Papers:

Effects and related mechanisms of serotonin on malignant biological behavior of hepatocellular carcinoma via regulation of Yap

Abstract