MMP1 expression is activated by Slug and enhances multi-drug resistance (MDR) in breast cancer

doi:10.1371/journal.pone.0174487

Chia Nan University of Pharmacy & Science Institutional Repository > 環境永續暨休閒學院 > 運動管理系 > 期刊論文 > Item 310902800/31761

jsp.display-item.identifier=請使用永久網址來引用或連結此文件: https://ir.cnu.edu.tw/handle/310902800/31761

標題:	MMP1 expression is activated by Slug and enhances multi-drug resistance (MDR) in breast cancer
作者:	Shen, Ching-Ju Kuo, Yu-Ling Chen, Chien-Chung Chen, Ming-Jenn Cheng, Ya-Min
貢獻者:	Kaohsiung Med Univ, Grad Inst Med Kaohsiung Med Univ,Kaohsiung Med Univ Hosp, Dept Gynecol & Obstet E Da Hosp, Dept Plast & Reconstruct Surg Chi Mei Med Ctr, Dept Surg Chia Nan Univ Pharm & Sci, Dept Sports Management Natl Cheng Kung Univ, Inst Clin Med, Dept Obstet & Gynecol
關鍵字:	Matrix-Metalloproteinase Mesenchymal Transition Signaling Pathway Cells Overexpression Contributes Metastasis Inhibition Prognosis Carcinoma
日期:	2017-03-23
上傳時間:	2018-11-30 15:55:42 (UTC+8)
出版者:	Public Library Science
摘要:	High matrix metalloproteinase 1 (MMP1) expression is associated with enhanced breast cancer growth and metastasis and also might predict poor prognosis. In this study, we further investigated the functional role of MMP1 and how it is upregulated in multi-drug resistant (MDR) breast cancer cells. By retrieving microarray data in GEO datasets and the survival data in the Kaplan Meier plotter, we observed that MMP1 is significantly upregulated in MCF-7/ADR cells compared to the parental MCF-7 cells, while high MMP1 expression is associated with worse overall survival (OS) and recurrence free survival (RFS) in breast cancer patients after systematic therapy. Functional studies showed that MMP1 overexpression significantly reduced the drug sensitivity in MCF-7 cells, while MMP1 knockdown substantially enhanced the sensitivity in MCF-7/ADR cells. By performing western blotting and immunofluorescent staining, we confirmed that MCF-7/ADR cells had enhanced mesenchymal properties than MCF-7 cells. In MCF-7 cells, enforced Slug expression resulted in significant MMP1 upregulation, while in MCF-7/ADR cells, Slug knockdown led to reduced MMP1 expression. By performing bioinformatic analysis, we observed that the promoter of MMP1 has three putative Slug binding sites. The following dual luciferase assay and ChIP-qPCR verified these three binding sites. Therefore, we infer that Slug enhances MMP1 transcription via directly binding to the promoter region in breast cancer cells, which is a previously unrecognized mechanism in the development of MDR.
關聯:	Plos One, v.12, n.3, e0174487
显示于类别:	[運動管理系] 期刊論文

文件中的档案:

档案	描述	大小	格式	浏览次数
10.1371-journal.pone.0174487.pdf		3708Kb	Adobe PDF	0	检视/开启
index.html		0Kb	HTML	1209	检视/开启

在CNU IR中所有的数据项都受到原著作权保护.

TAIR相关文章

数据加载中.....