Theranostics 2016; 6(4):533-544. doi:10.7150/thno.14315
Mifepristone Suppresses Basal Triple-Negative Breast Cancer Stem Cells by Down-regulating KLF5 Expression
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;
2. Department of Neurology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China;
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 of Science & Technology of China, Hefei, Anhui, 230027, China.
Liu R, Shi P, Nie Z, Liang H, Zhou Z, Chen W, Chen H, Dong C, Yang R, Liu S, Chen C. Mifepristone Suppresses Basal Triple-Negative Breast Cancer Stem Cells by Down-regulating KLF5 Expression. Theranostics 2016; 6(4):533-544. doi:10.7150/thno.14315. Available from http://www.thno.org/v06p0533.htm
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.
Keywords: Triple-negative Breast Cancer, Mifepristone, Cancer Stem Cell, KLF5, miR-153.