Cancer Communications
indexed by SCI
BMC

Original article
NS1-binding protein radiosensitizes esophageal squamous cell carcinoma by transcriptionally suppressing c-Myc
Yuwen Wang, Jingjing Cheng, Dan Xie, Xiaofeng Ding, Hailing Hou, Xi Chen, Puchun Er, Furong Zhang, Lujun Zhao, Zhiyong Yuan, Qingsong Pang, Ping Wang and Dong Qian
Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, P. R. China; National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, P. R. China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin, P. R. China
[Abstract]

Background
Cisplatin-based chemotherapy with concurrent radiotherapy is a standard treatment for advanced esophageal squamous cell carcinoma (ESCC). NS1-binding protein (NS1-BP), a member of the BTB-kelch protein family, has been shown to inhibit the proliferation of Hela cells by suppressing c-Myc. In the present study, we examined the potential function role of NS1-BP expression in ESCC, and particularly, the sensitivity of ESCC to radiotherapy.
Methods
NS1-BP expression was examined using immunohistochemistry in two cohorts (n?=?98 for the training cohort; n?=?46 for independent validation cohort) of ESCC patients receiving cisplatin-based chemotherapy and concurrent radiotherapy. Normal esophageal mucosal tissue blocks were used as a control. We also conducted a series of in vitro and in vivo experiments to examine the potential effects of over-expressing NS1-BP on ESCC cells, and particularly their sensitivity to ionizing irradiation.
Results
In the training cohort, NS1-BP downregulation was observed in 59% (85/144) of the ESCC specimens. NS1-BP downregulation was associated with chemoradiotherapeutic resistance and shorter disease-specific survival (DSS) in both the training and validation cohorts. Over-expressing NS1-BP in cultured ESCC cells substantially increased the cellular response to irradiation both in vitro and in vivo. NS1-BP also significantly enhanced IR-induced apoptosis, and abrogated IR-induced G2/M cell-cycle arrest and ATM/Chk1 phosphorylation. Immunoprecipitation assays indicated that NS1-BP could interact with c-Myc promoter regions to inhibit its transcription. In ESCC tissues, c-Myc expression was inversely correlated with NS1-BP levels, and was associated with a shorter DSS.
Conclusions
Our findings highlight the role and importance of NS1-BP in radiosensitivity of ESCC. Targeting the NS1-BP/c-Myc pathway may provide a novel therapeutic strategy for ESCC.
Cancer Communications   Epub date: 2018-6-5   doi:10.1186/s40880-018-0307-y   [ PDF Full-text ]   


 

Editorial Manager


CC adopts Editorial Manager to manage its submissions from Dec.18, 2014

 Submission Guidelines  

 

Reference style for  

 EndNote,
 Reference Manager



Editorial Manager


 

Year:

 

Month:

Advanced search

Subscription


CC is now published by BioMed Central

© Cancer Communications

651 Dongfeng Road East, Guangzhou 510060, P. R. China