UCH-L1-mediated Down-regulation of Estrogen Receptor alpha Contributes to Insensitivity to Endocrine Therapy for Breast Cancer

KIZ OpenIR > 科研部门 > 肿瘤生物学（陈策实）

	UCH-L1-mediated Down-regulation of Estrogen Receptor alpha Contributes to Insensitivity to Endocrine Therapy for Breast Cancer
	Chen, Xi-Sha; Wang, Kuan-Song; Guo, Wei; Li, Lan-Ya; Yu, Pian; Sun, Xin-Yuan; Wang, Hai-Yan; Guan, Yi-Di; Tao, Yong-Guang; Ding, Bo-Ni; Yin, Ming-Zhu; Ren, Xing-Cong; Zhang, Yi; Chen, Ce-Shi; Ye, Yuan-Chao; Yang, Jin-Ming; Cheng, Yan
	2020
发表期刊	THERANOSTICS
ISSN	1838-7640
卷号	10 期号:4 页码:1833-1848
摘要	Purpose: To determine the role of UCH-L1 in regulating ER alpha expression, and to evaluate whether therapeutic targeting of UCH-L1 can enhance the efficacy of anti-estrogen therapy against breast cancer with loss or reduction of ER alpha.Methods: Expressions of UCH-L1 and ER alpha were examined in breast cancer cells and patient specimens. The associations between UCH-L1 and ER alpha, therapeutic response and prognosis in breast cancer patients were analyzed using multiple databases. The molecular pathways by which UCH-L1 regulates ER alpha were analyzed using immunoblotting, qRT-PCR, immunoprecipitation, ubiquitination, luciferase and ChIP assays. The effects of UCH-L1 inhibition on the efficacy of tamoxifen in ER alpha (-) breast cancer cells were tested both in vivo and in vitro.Results: UCH-L1 expression was conversely correlated with ER alpha status in breast cancer, and the negative regulatory effect of UCH-L1 on ER alpha was mediated by the deubiquitinase-mediated stability of EGFR, which suppresses ER alpha transcription. High expression of UCH-L1 was associated with poor therapeutic response and prognosis in patients with breast cancer. Up-regulation of ER alpha caused by UCH-L1 inhibition could significantly enhance the efficacy of tamoxifen and fulvestrant in ER alpha (-) breast cancer both in vivo and in vitro.Conclusions: Our results reveal an important role of UCH-L1 in modulating ER alpha status and demonstrate the involvement of UCH-L1-EGFR signaling pathway, suggesting that UCH-L1 may serve as a novel adjuvant target for treatment of hormone therapy-insensitive breast cancers. Targeting UCH-L1 to sensitize ER negative breast cancer to anti-estrogen therapy might represent a new therapeutic strategy that warrants further exploration.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/12885
专题	科研部门_肿瘤生物学（陈策实）
推荐引用方式 GB/T 7714	Chen, Xi-Sha,Wang, Kuan-Song,Guo, Wei,et al. UCH-L1-mediated Down-regulation of Estrogen Receptor alpha Contributes to Insensitivity to Endocrine Therapy for Breast Cancer[J]. THERANOSTICS,2020,10(4):1833-1848.
APA	Chen, Xi-Sha.,Wang, Kuan-Song.,Guo, Wei.,Li, Lan-Ya.,Yu, Pian.,...&Cheng, Yan.(2020).UCH-L1-mediated Down-regulation of Estrogen Receptor alpha Contributes to Insensitivity to Endocrine Therapy for Breast Cancer.THERANOSTICS,10(4),1833-1848.
MLA	Chen, Xi-Sha,et al."UCH-L1-mediated Down-regulation of Estrogen Receptor alpha Contributes to Insensitivity to Endocrine Therapy for Breast Cancer".THERANOSTICS 10.4(2020):1833-1848.

条目包含的文件
文件名称/大小	文献类型	版本类型	开放类型	使用许可
2021110112.pdf（3403KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	请求全文