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Mifepristone Suppresses Basal Triple-Negative Breast Cancer Stem Cells by Down-regulating KLF5 Expression

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 bre...

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Autores principales: Liu, Rong, Shi, Peiguo, Nie, Zhi, Liang, Huichun, Zhou, Zhongmei, Chen, Wenlin, Chen, Haijun, Dong, Chao, Yang, Runxiang, Liu, Suling, Chen, Ceshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4775863/
https://www.ncbi.nlm.nih.gov/pubmed/26941846
http://dx.doi.org/10.7150/thno.14315
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author Liu, Rong
Shi, Peiguo
Nie, Zhi
Liang, Huichun
Zhou, Zhongmei
Chen, Wenlin
Chen, Haijun
Dong, Chao
Yang, Runxiang
Liu, Suling
Chen, Ceshi
author_facet Liu, Rong
Shi, Peiguo
Nie, Zhi
Liang, Huichun
Zhou, Zhongmei
Chen, Wenlin
Chen, Haijun
Dong, Chao
Yang, Runxiang
Liu, Suling
Chen, Ceshi
author_sort Liu, Rong
collection PubMed
description 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.
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spelling pubmed-47758632016-03-03 Mifepristone Suppresses Basal Triple-Negative Breast Cancer Stem Cells by Down-regulating KLF5 Expression Liu, Rong Shi, Peiguo Nie, Zhi Liang, Huichun Zhou, Zhongmei Chen, Wenlin Chen, Haijun Dong, Chao Yang, Runxiang Liu, Suling Chen, Ceshi Theranostics Research Paper 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. Ivyspring International Publisher 2016-02-13 /pmc/articles/PMC4775863/ /pubmed/26941846 http://dx.doi.org/10.7150/thno.14315 Text en © Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions.
spellingShingle Research Paper
Liu, Rong
Shi, Peiguo
Nie, Zhi
Liang, Huichun
Zhou, Zhongmei
Chen, Wenlin
Chen, Haijun
Dong, Chao
Yang, Runxiang
Liu, Suling
Chen, Ceshi
Mifepristone Suppresses Basal Triple-Negative Breast Cancer Stem Cells by Down-regulating KLF5 Expression
title Mifepristone Suppresses Basal Triple-Negative Breast Cancer Stem Cells by Down-regulating KLF5 Expression
title_full Mifepristone Suppresses Basal Triple-Negative Breast Cancer Stem Cells by Down-regulating KLF5 Expression
title_fullStr Mifepristone Suppresses Basal Triple-Negative Breast Cancer Stem Cells by Down-regulating KLF5 Expression
title_full_unstemmed Mifepristone Suppresses Basal Triple-Negative Breast Cancer Stem Cells by Down-regulating KLF5 Expression
title_short Mifepristone Suppresses Basal Triple-Negative Breast Cancer Stem Cells by Down-regulating KLF5 Expression
title_sort mifepristone suppresses basal triple-negative breast cancer stem cells by down-regulating klf5 expression
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4775863/
https://www.ncbi.nlm.nih.gov/pubmed/26941846
http://dx.doi.org/10.7150/thno.14315
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