title: Ring finger protein 6 promotes breast cancer cell proliferation by stabilizing estrogen receptor alpha.
abstract: 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.
authors.affiliation: Jiangsu 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.|Department of Oncology, Suzhou Municipal Hospital East Campus, Suzhou, 215100, P.R. China.
authors.forename: Yuanying
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Jiangsu 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.|Suzhou Institute of Systems Medicine, Center of Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, 215123, P. R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.affiliation: Jiangsu 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.
authors.forename: Siyu
authors.initials: S
authors.lastname: Wang
authors.affiliation: Jiangsu 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.
authors.forename: Zubin
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Jiangsu 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.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Jiangsu 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.
authors.forename: Kunkun
authors.initials: K
authors.lastname: Han
authors.affiliation: Jiangsu 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.
authors.forename: Biyin
authors.initials: B
authors.lastname: Cao
authors.affiliation: Jiangsu 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.|Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, 215123, P. R. China.|Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 511436, P. R. China.
authors.forename: Xinliang
authors.initials: X
authors.lastname: Mao
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D016022:Case-Control Studies; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C494811:BCL2L1 protein, human; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D047628:Estrogen Receptor alpha; C119753:RNF6 protein, human; D051020:bcl-X Protein
keywords: Bcl-xL; ERα; breast cancer; doxorubicin; ring finger protein 6