COPS5 inhibition arrests the proliferation and growth of serous ovarian cancer cells via the elevation of p27 level

Hongqin Zhang; Ailing Zhong; Jiajun Sun; Miaomiao Chen; Suhong Xie; Hui Zheng; Yanchun Wang; Yiwen Yu; Lin Guo; Renquan Lu

doi:10.1016/j.bbrc.2017.09.070

COPS5 inhibition arrests the proliferation and growth of serous ovarian cancer cells via the elevation of p27 level

Biochem Biophys Res Commun. 2017 Nov 4;493(1):85-93. doi: 10.1016/j.bbrc.2017.09.070. Epub 2017 Sep 15.

Authors

Affiliations

¹ Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China.
² Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China.
³ Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China. Electronic address: lurenquan@126.com.

PMID: 28919423
DOI: 10.1016/j.bbrc.2017.09.070

Abstract

The fifth component of the COP9 signalosome complex (COPS5), which plays an essential role in ubiquitin-mediated protein degradation, has been found as a prognostic biomarker for multiple cancers, however, the role of COPS5 in serous ovarian cancer (SOC) remain to be clarified. In this study, we found that COPS5 expression was significantly increased in SOC cells and tissues compared with those controls. Mechanistically, COPS5 and p27was proved to interact with each other, with COPS5 acts as a negative regulator of p27. SOC cells with COPS5 depletion were arrested in G1/G0-phase and exhibited a reduced proliferation ability and an increased cytoplasmic p27 expression. Whereas, the cells were stuck at S-phase accompanied with an elevation of nucleus p27 expression after knocking down COPS6 or blocking COPS5 by CSN5i-3. Furthermore, inhibition of COPS5 resulted in an elevation of Akt expression and sensitized SOC cells to Akt inhibitor MK2206. Suppression of COPS5 and Akt offers a potential strategy for the treatment of SOC.

Keywords: Akt; COPS5; COPS6; Serous ovarian cancer; p27.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COP9 Signalosome Complex
Cell Cycle Checkpoints
Cell Proliferation*
Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
Cystadenocarcinoma, Serous / metabolism*
Cystadenocarcinoma, Serous / pathology*
Female
Humans
Intracellular Signaling Peptides and Proteins / metabolism*
Ovarian Neoplasms / metabolism*
Ovarian Neoplasms / pathology*
Peptide Hydrolases / metabolism*
Tumor Cells, Cultured

Substances

Intracellular Signaling Peptides and Proteins
Cyclin-Dependent Kinase Inhibitor p27
Peptide Hydrolases
COPS5 protein, human
COP9 Signalosome Complex