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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2017

Open Access 01-12-2017 | Research

Over-expression of BAG-1 in head and neck squamous cell carcinomas (HNSCC) is associated with cisplatin-resistance

Authors: Shutong Liu, Bo Ren, Hang Gao, Suchan Liao, Ying-Xian Zhai, Shirong Li, Xue-Jin Su, Ping Jin, David Stroncek, Zhixiang Xu, Qinghua Zeng, Yulin Li

Published in: Journal of Translational Medicine | Issue 1/2017

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Abstract

Background

In order to improve therapy for head and neck squamous cell carcinoma (HNSCC), biomarkers associated with local and/or distant tumor relapses and cancer drug resistance are urgently needed. This study identified a potential biomarker, Bcl-2 associated athanogene-1 (BAG-1), that is implicated in HNSCC insensitive to cisplatin and tumor progression.

Methods

Primary and advanced (relapsed from parental) University of Michigan squamous cell carcinoma cell lines were tested for sensitivity to cisplatin and gene expression profiles were compared between primary (cisplatin sensitive) and the relapsed (cisplatin resistant) cell lines by using Agilent microarrays. Additionally, differentially expressed genes phosphorylated AKT, and BAG-1, and BCL-xL were evaluated for expression using HNSCC tissue arrays.

Results

Advanced HNSCC cells revealed resistant to cisplatin accompanied by increased expression of BAG-1 protein. siRNA knockdown of BAG-1 expression resulted in significant improvement of HNSCC sensitivity to cisplatin. BAG-1 expression enhanced stability of BCL-xL and conferred cisplatin resistant to the HNSCC cells. In addition, high levels of expression of phosphorylated AKT, BAG-1, and BCL-xL were observed in advanced HNSCC compared to in that of primary HNSCC.

Conclusion

Increased expression of BAG-1 was associated with cisplatin resistance and tumor progression in HNSCC patients and warrants further validation in larger independent studies. Over expression of BAG-1 may be a biomarker for cisplatin resistance in patients with primary or recurrent HNSCCs and targeting BAG-1 could be helpful in overcoming cisplatin resistance.
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Metadata
Title
Over-expression of BAG-1 in head and neck squamous cell carcinomas (HNSCC) is associated with cisplatin-resistance
Authors
Shutong Liu
Bo Ren
Hang Gao
Suchan Liao
Ying-Xian Zhai
Shirong Li
Xue-Jin Su
Ping Jin
David Stroncek
Zhixiang Xu
Qinghua Zeng
Yulin Li
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2017
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-017-1289-2

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