Oncotarget

Research Papers:

Derlin-1 is a target to improve radiotherapy effect of esophageal squamous cell carcinoma

Qianze Dong, Lin Fu, Yue Zhao _, Yang Liu, Qingchang Li, Xueshan Qiu and Enhua Wang

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Oncotarget. 2017; 8:55135-55146. https://doi.org/10.18632/oncotarget.19069

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Abstract

Qianze Dong1,*, Lin Fu1,*, Yue Zhao1, Yang Liu1, Qingchang Li1, Xueshan Qiu1 and Enhua Wang1

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

*These authors contributed equally to this work

Correspondence to:

Yue Zhao, email: [email protected]

Keywords: Derlin-1, esophageal squamous cell carcinoma, AKT, radiotherapy

Received: January 09, 2017     Accepted: June 18, 2017     Published: July 07, 2017

ABSTRACT

Radiotherapy is widely used for treatment of esophageal squamous cell carcinoma (ESCC). This study aimed to explore the role of Derlin-1 on the sensitivity of ESCC to radiotherapy and its underlying mechanism. We examined the clinical significance of Derlin-1 in 125 ESCC tissues. We found that Derlin-1 protein was higher in ESCC tissues than that in normal esophageal epithelial tissues. Derlin-1 overexpression was correlated with chemoradiotherapy resistance in ESCC patients and served an independent predictor for short overall survival. siRNA knockdown and plasmid transfection were carried out in ESCC cell lines. Derlin-1 depletion inhibited cell growth while its overexpression facilitated cell growth. Derlin-1 overexpression in Eca-109 cells dramatically enhanced its resistance to radiotherapy with decreased apoptosis rate. On the contrary, Derlin-1 depletion in TE-1 cell line showed the opposite effects. In addition, radioresistance conferred by Derlin-1 was attributed to its role of activating AKT/Bcl-2 signaling pathway and reducing caspase3 cleavage. Blockage of AKT signaling attenuated the role of Derlin-1 on radioresistance. Furthermore, Derlin-1 could interact with PI3K p110α in ESCC cell lines. Taken together, Our data demonstrate that Derlin-1 overexpression predicts poor prognosis and protects ESCC from irradiation induced apoptosis through PI3K/AKT/Bcl-2 signaling pathway. Derlin-1 may serve as a novel predictor for radiosentivity and a molecular target for ESCC.


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