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

Qianze Dong | Zendy; Lin Fu | Zendy; Yue Zhao | Zendy; Shutao Tan | Zendy; Enhua Wang | Zendy

Open Access

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

Author(s) -

Qianze Dong,

Lin Fu,

Yue Zhao,

Shutao Tan,

Enhua Wang

Publication year - 2017

Publication title -

oncotarget

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.373

H-Index - 127

ISSN - 1949-2553

DOI - 10.18632/oncotarget.15001

Subject(s) - downregulation and upregulation , protein kinase b , bladder cancer , pi3k/akt/mtor pathway , cancer research , medicine , cisplatin , mapk/erk pathway , cancer , phosphorylation , cell growth , signal transduction , biology , chemotherapy , microbiology and biotechnology , biochemistry , gene

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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