机构：[1]Kunming Institute of Zoology, Chinese Academy of Sciences, Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy ofSciences & Yunnan Province, Kunming, 650223, China[2]Department of Neurology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China昆明医科大学附属第一医院[3]Department of Breast surgery, the 3rd affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650118, China[4]College of Chemistry and Chemical Engineering, Fuzhou University, Fuzhou, 350108, China[5]Department of the second medical oncology, the 3rd affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650118, China[6]Institute for Cancer Research, CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University ofScience & Technology of China, Hefei, Anhui, 230027, China.
Triple-negative breast cancer (TNBC) is currently the most malignant subtype of breast cancers without effective targeted therapies. Mifepristone (MIF), a drug regularly used for abortion, has been reported to have anti-tumor activity in multiple hormone-dependent cancers, including luminal type breast cancers. In this study, we showed that MIF suppressed tumor growth of the TNBC cell lines and patient-derived xenografts in NOD-SCID mice. Furthermore, MIF reduced the TNBC cancer stem cell (CSC) population through down-regulating KLF5 expression, a stem cell transcription factor over-expressed in basal type TNBC and promoting cell proliferation, survival and stemness. Interestingly, MIF suppresses the expression of KLF5 through inducing the expression of miR-153. Consistently, miR-153 decreases CSC and miR-153 inhibitor rescued MIF-induced down-regulation of the KLF5 protein level and CSC ratio. Taken together, our findings suggest that MIF inhibits basal TNBC via the miR-153/KLF5 axis and MIF may be used for the treatment of TNBC.
基金：
Strategic Priority Research Program of the Chinese Academy of Sciences, Stem Cell and Regenerative Medicine Research [XDA01040406]; National Nature Science Foundation of ChinaNational Natural Science Foundation of China [81322038, 81272930, 81325016, 81120108019, U1132605, U1502222]; Yunnan Applied Basic Research Key Projects [2015FA027]; West Light Foundation of Chinese Academy of SciencesChinese Academy of Sciences; Youth Innovation Promotion Association, Chinese Academy of Sciences; Changsha Science and Technology Program Key Projects [K1406209-31]
第一作者机构：[1]Kunming Institute of Zoology, Chinese Academy of Sciences, Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy ofSciences & Yunnan Province, Kunming, 650223, China
通讯作者：
推荐引用方式(GB/T 7714)：
Liu Rong,Shi Peiguo,Nie Zhi,et al.Mifepristone Suppresses Basal Triple-Negative Breast Cancer Stem Cells by Down-regulating KLF5 Expression[J].THERANOSTICS.2016,6(4):533-544.doi:10.7150/thno.14315.
APA：
Liu, Rong,Shi, Peiguo,Nie, Zhi,Liang, Huichun,Zhou, Zhongmei...&Chen, Ceshi.(2016).Mifepristone Suppresses Basal Triple-Negative Breast Cancer Stem Cells by Down-regulating KLF5 Expression.THERANOSTICS,6,(4)
MLA：
Liu, Rong,et al."Mifepristone Suppresses Basal Triple-Negative Breast Cancer Stem Cells by Down-regulating KLF5 Expression".THERANOSTICS 6..4(2016):533-544
医学