Oncotarget

Research Papers:

Derlin-1 overexpression confers poor prognosis in muscle invasive bladder cancer and contributes to chemoresistance and invasion through PI3K/AKT and ERK/MMP signaling

Qianze Dong, Lin Fu, Yue Zhao, Shutao Tan and Enhua Wang _

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Oncotarget. 2017; 8:17059-17069. https://doi.org/10.18632/oncotarget.15001

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Abstract

Qianze Dong1, Lin Fu1, Yue Zhao1, Shutao Tan2, Enhua Wang1

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

2Department of Urology, Shengjing Hospital of China Medical University, Shenyang, China

Correspondence to:

Enhua Wang, email: wangenhuacmu@hotmail.com

Keywords: Derlin-1, bladder cancer, prognosis, ERK, AKT

Received: October 06, 2016    Accepted: January 04, 2017    Published: February 02, 2017

ABSTRACT

Derlin-1 has been found to be overexpressed in several human cancers. However, its clinical significance and biological roles in bladder cancer remain unexplored. Here, we found that Derlin-1 was upregulated in 38.6% (58/150) cases of cancer samples. The rate of Derlin-1 overexpression was higher in muscle invasive bladder cancer (MIBC) than non-muscle invasive bladder cancer (NMIBC) (p=0.0079). Derlin-1 was a predicting factor for poor patient prognosis. Derlin-1 depletion inhibited while its overexpression facilitated cell invasion and colony formation. In addition, Derlin-1 overexpression induced cisplatin resistance while its depletion sensitized cancer cells to cisplatin. Further analysis demonstrated that Derlin-1 activated AKT phosphorylation and upregulated Bcl-2 expression. Blockage of AKT signaling by LY294005 abolished the effects of Derlin-1 on Bcl-2 and cisplatin resistance. Immunoprecipitation indicated Derlin-1 interacted with p110α subunit of PI3K. In addition, we showed that Derlin-1 depletion downregulated and its overexpression upregulated cell MMP-2/9 expression and ERK phosphorylation. Derlin-1 mediated upregulation of MMP-2/9 could be blocked by ERK inhibitor. In conclusion, our study demonstrated that Derlin-1 is overexpressed in bladder cancer and promotes malignant phenotype through ERK/MMP and PI3K/AKT/Bcl-2 signaling pathway.


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