Oncotarget

Research Papers:

DEPTOR suppresses the progression of esophageal squamous cell carcinoma and predicts poor prognosis

Yan-Mei Ji, Xue-Feng Zhou, Jun Zhang, Xiang Zheng, Sheng-Bao Li, Zhi-Qiang Wei, Tao Liu, Dong-Liang Cheng, Ping Liu, Kuncheng Song, Tao Tan, Hua Zhu and Jia-Long Guo _

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Oncotarget. 2016; 7:14188-14198. https://doi.org/10.18632/oncotarget.7420

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Abstract

Yan-Mei Ji1,*, Xue-Feng Zhou2,*, Jun Zhang3,*, Xiang Zheng1, Sheng-Bao Li4, Zhi-Qiang Wei5, Tao Liu4, Dong-Liang Cheng3, Ping Liu6, Kuncheng Song7, Tao Tan7, Hua Zhu7, Jia-Long Guo3

1Department of Intensive Care Unit, Taihe Hospital, Hubei University of Medicine, Shiyan, People’s Republic of China

2Department of Thoracic and Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China

3Department of Cardiothoracic Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan, People’s Republic of China

4Department of Gastroenterology, Taihe Hospital, Hubei University of Medicine, Shiyan, People’s Republic of China

5Institute of Biomedical Research, Taihe Hospital, Hubei University of Medicine, Shiyan, People’s Republic of China

6Department of Pathology, Taihe Hospital, Hubei University of Medicine, Shiyan, People’s Republic of China

7Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, The United States

*These authors contributed equally to this work

Correspondence to:

Jia-Long Guo, e-mail: [email protected]

Hua Zhu, e-mail: [email protected]

Keywords: DEPTOR, mTOR, esophageal squamous cell carcinoma, proliferation

Received: November 09, 2015     Accepted: January 29, 2016     Published: February 16, 2016

ABSTRACT

As a naturally occurring inhibitor of mTOR, accumulated evidence has suggested that DEPTOR plays a pivotal role in suppressing the progression of human malignances. However, the function of DEPTOR in the development of esophageal squamous cell carcinoma (ESCC) is still unclear. Here we report that the expression of DEPTOR is significantly reduced in tumor tissues derived from human patients with ESCC, and the downregulation of DEPTOR predicts a poor prognosis of ESCC patients. In addition, we found that the expression of DEPTOR negatively regulates the tumorigenic activities of ESCC cell lines (KYSE150, KYSE510 and KYSE190). Furthermore, ectopic DEPTOR expression caused a significant suppression of the cellular proliferation, migration and invasion of KYSE150 cells, which has the lowest expression level of DEPTOR in the three cell lines. Meanwhile, CRISPR/Cas9 mediated knockout of DEPTOR in KYSE-510 cells significantly promoted cellular proliferation, migration and invasion. In addition, in vivo assays further revealed that tumor growth was significantly inhibited in xenografts with ectopic DEPTOR expression as compared to untreated KYSE150 cells, and was markedly enhanced in DEPTOR knockout KYSE-510 cells. Biochemical studies revealed that overexpression of DEPTOR led to the suppression of AKT/mTOR pathway as evidenced by reduced phosphorylation of AKT, mTOR and downstream SGK1, indicating DEPTOR might control the progression of ESCC through AKT/mTOR signaling pathway. Thus, these findings, for the first time, demonstrated that DEPTOR inhibits the tumorigenesis of ESCC cells and might serve as a potential therapeutic target or prognostic marker for human patients with ESCC.


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