期刊
NEOPLASIA
卷 22, 期 9, 页码 343-351出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neo.2020.06.003
关键词
Breast cancer; ER alpha; TRIM11; Mono-ubiquitination; Polyubiquitination
类别
资金
- Research and Development Fund of Zhongnan Hospital of Wuhan University [20170101]
Breast cancer is the most commonly diagnosed malignancy in female worldwide, over 70% of which are estrogen receptor alpha (ER alpha) positive. ER alpha has a crucial role in the initiation and progression of breast cancer and is an indicator of endocrine therapy, while endocrine resistance is an urgent problem in ER-positive breast cancer patients. In the present study, we identify a novel E3 ubiquitin ligase TRIM11 function to facilitate ERa signaling. TRIM11 is overexpressed in human breast cancer, and associates with poor prognosis. The protein level of TRIM11 is highly correlated with ER alpha. RNA-seq results suggest that ER alpha signaling may be an underlying target of TRIM11. Depletion of TRIM11 in breast cancer cells significantly decreases cell proliferation and migration. And the suppression effects can be reversed by overexpressing ER alpha. In addition, ER alpha protein level, ER alpha target genes expression and estrogen response element activity are also dramatically decreased by TRIM11 depletion. Further mechanistic analysis indicates that the RING domain of TRIM11 interacted with the N terminal of ER alpha in the cytoplasm and promotes its mono-ubiquitination, thus enhances ER alpha protein stability. Our study describes TRIM11 as a modulating factor of ER alpha and increases ER alpha stability via mono-ubiquitination. TRIM11 could be a promising therapeutic target for breast cancer treatment.
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