Ring finger protein 6 promotes breast cancer cell proliferation by stabilizing estrogen receptor alpha
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Yuanying Zeng1,2,*, Xin Xu1,3,*, Siyu Wang1,*, Zubin Zhang1, Yan Liu1, Kunkun Han1, Biyin Cao1, Xinliang Mao1,4,5
1Jiangsu Key Laboratory for Translational Research and Therapeutics of Neuro-Psycho- Diseases, Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, 215123, P. R. China
2Department of Oncology, Suzhou Municipal Hospital East Campus, Suzhou, 215100, P.R. China
3Suzhou Institute of Systems Medicine, Center of Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, 215123, P. R. China
4Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, 215123, P. R. China
5Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 511436, P. R. China
*These authors have contributed equally to this work
Yuanying Zeng, email: zengyu[email protected]
Xinliang Mao, email: [email protected]
Keywords: ring finger protein 6, breast cancer, ERα, Bcl-xL, doxorubicin
Received: November 30, 2016 Accepted: January 22, 2017 Published: February 16, 2017
Ring finger protein 6 (RNF6) is a key oncogene in both prostate cancer and leukemia, but its role is elusive in breast cancer. In the present study, we found that RNF6 was overexpressed in more than 70% of breast cancer tissues and it was associated with overall survival. RNF6 increased breast cancer cell proliferation, migration and reduced cell sensitivity to doxorubicin. Further studies showed that RNF6 was closely associated with increased expression of estrogen receptor, a critical factor in the development of breast cancers. RNF6 was found to induce ERα expression and increased its stability. In doxorubicin-resistant breast cancer cells, RNF6 was found to be elevated in association with increased ERα and anti-apoptotic Bcl-xL, but not pro-apoptotic Bim-1. In consistence with this finding, overexpression of ERα led to increased Bcl-xL but had no effects on Bim-1. Therefore, this study demonstrated that there exists an RNF6/ERα/Bcl-xL axle in breast cancer which promotes cancer cell proliferation and survival. Targeting the RNF6/ERα/Bcl-xL axle could be a promising strategy in the treatment of breast cancer.
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