title: Mifepristone Suppresses Basal Triple-Negative Breast Cancer Stem Cells by Down-regulating KLF5 Expression.
abstract: 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.
authors.affiliation: 1. Kunming Institute of Zoology, Chinese Academy of Sciences, Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming, 650223, China;
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.affiliation: 1. Kunming Institute of Zoology, Chinese Academy of Sciences, Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming, 650223, China;
authors.forename: Peiguo
authors.initials: P
authors.lastname: Shi
authors.affiliation: 2. Department of Neurology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China;
authors.forename: Zhi
authors.initials: Z
authors.lastname: Nie
authors.affiliation: 1. Kunming Institute of Zoology, Chinese Academy of Sciences, Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming, 650223, China;
authors.forename: Huichun
authors.initials: H
authors.lastname: Liang
authors.affiliation: 1. Kunming Institute of Zoology, Chinese Academy of Sciences, Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming, 650223, China;
authors.forename: Zhongmei
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: 3. Department of Breast surgery, the 3rd affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650118, China;
authors.forename: Wenlin
authors.initials: W
authors.lastname: Chen
authors.affiliation: 4. College of Chemistry and Chemical Engineering, Fuzhou University, Fuzhou, 350108, China;
authors.forename: Haijun
authors.initials: H
authors.lastname: Chen
authors.affiliation: 5. Department of the second medical oncology, the 3rd affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650118, China;
authors.forename: Chao
authors.initials: C
authors.lastname: Dong
authors.affiliation: 5. Department of the second medical oncology, the 3rd affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650118, China;
authors.forename: Runxiang
authors.initials: R
authors.lastname: Yang
authors.affiliation: 6. Institute for Cancer Research, CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei, Anhui, 230027, China.
authors.forename: Suling
authors.initials: S
authors.lastname: Liu
authors.affiliation: 1. Kunming Institute of Zoology, Chinese Academy of Sciences, Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming, 650223, China;
authors.forename: Ceshi
authors.initials: C
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects*; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D064593:Heterografts; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000037:antagonists & inhibitors*; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D035683:MicroRNAs / Q000096:biosynthesis; D015735:Mifepristone / Q000494:pharmacology* / Q000627:therapeutic use; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; C492214:KLF5 protein, human; D051741:Kruppel-Like Transcription Factors; C556500:MIRN153 microRNA, human; D035683:MicroRNAs; D015735:Mifepristone
keywords: Cancer Stem Cell; KLF5; Mifepristone; Triple-negative Breast Cancer; miR-153.