COP9 signalosome subunit 5 regulates cancer metastasis by deubiquitinating SNAIL

Oncotarget
Kensuke WatanabeIkuo Saiki

Abstract

Cancer metastasis is a major cause of mortality in cancer patients. The transcription factor SNAIL plays an important role in cancer metastasis and progression, and its expression is tightly regulated by the ubiquitin-proteasome system through the balance between ubiquitin ligases and deubiquitinating enzymes. While several ubiquitin ligases of SNAIL have been identified, it is not yet clear regarding deubiquitinating enzyme. In this study, we identified COP9 signalosome subunit 5 (COPS5) as a deubiquitinating enzyme of SNAIL by using siRNA library screening. COPS5 downregulation significantly reduced the expression of SNAIL and impaired the metastatic potential of lung cancer cells both in vitro and in vivo. Importantly, we demonstrated that COPS5 binds to SNAIL and stabilizes its expression by deubiquitination. Furthermore, we observed the positive correlation between COPS5 and SNAIL expression in the clinical tissue samples of lung adenocarcinomas by using tissue microarray analysis. These findings provide strong evidence that COPS5 can be a new therapeutic target for cancer metastasis as a deubiquitinating enzyme of SNAIL.

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Citations

Aug 27, 2019·Biochimica Et Biophysica Acta. Reviews on Cancer·Ji ChengWenyi Wei
Nov 7, 2020·Scientific Reports·Satoru YokoyamaHiroaki Sakurai

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Methods Mentioned

BETA
ubiquitination
deubiquitination
immunoprecipitation
co-immunoprecipitation
transfection

Software Mentioned

Prognoscan
ImageJ
GraphPad
Graphpad Prism

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