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DLG5 suppresses breast cancer stem cell‐like characteristics to restore tamoxifen sensitivity by inhibiting TAZ expression

Tamoxifen (TAM) is a primary drug for treatment of estrogen receptor positive breast cancer. However, TAM resistance remains a serious threat to breast cancer patients and may be attributed to increased stemness of breast cancer. Here, we show that discs large homolog 5 (DLG5) expression is down‐reg...

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Detalles Bibliográficos
Autores principales: Liu, Jie, Li, Juan, Li, Pingping, Jiang, Yina, Chen, He, Wang, Ruiqi, Cao, Fang, Liu, Peijun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307757/
https://www.ncbi.nlm.nih.gov/pubmed/30450766
http://dx.doi.org/10.1111/jcmm.13954
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author Liu, Jie
Li, Juan
Li, Pingping
Jiang, Yina
Chen, He
Wang, Ruiqi
Cao, Fang
Liu, Peijun
author_facet Liu, Jie
Li, Juan
Li, Pingping
Jiang, Yina
Chen, He
Wang, Ruiqi
Cao, Fang
Liu, Peijun
author_sort Liu, Jie
collection PubMed
description Tamoxifen (TAM) is a primary drug for treatment of estrogen receptor positive breast cancer. However, TAM resistance remains a serious threat to breast cancer patients and may be attributed to increased stemness of breast cancer. Here, we show that discs large homolog 5 (DLG5) expression is down‐regulated in TAM‐resistant breast cancer and cells. DLG5 silencing decreased the sensitivity to TAM and increased the frequency and stemness of CD44(+)/CD24(−) breast cancer stem cells (BCSCs) and TAZ, a transducer of the Hippo pathway, expression in MCF7 cells while DLG5 overexpression had opposite effects. TAZ silencing restored the sensitivity to TAM and reduced the frequency and stemness in TAM‐resistant breast cancer cells. Taken together, our data indicate that down‐regulated DLG5 expression increases the stemness of breast cancer cells by enhancing TAZ expression, contributing to TAM resistance in breast cancer.
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spelling pubmed-63077572019-01-04 DLG5 suppresses breast cancer stem cell‐like characteristics to restore tamoxifen sensitivity by inhibiting TAZ expression Liu, Jie Li, Juan Li, Pingping Jiang, Yina Chen, He Wang, Ruiqi Cao, Fang Liu, Peijun J Cell Mol Med Original Articles Tamoxifen (TAM) is a primary drug for treatment of estrogen receptor positive breast cancer. However, TAM resistance remains a serious threat to breast cancer patients and may be attributed to increased stemness of breast cancer. Here, we show that discs large homolog 5 (DLG5) expression is down‐regulated in TAM‐resistant breast cancer and cells. DLG5 silencing decreased the sensitivity to TAM and increased the frequency and stemness of CD44(+)/CD24(−) breast cancer stem cells (BCSCs) and TAZ, a transducer of the Hippo pathway, expression in MCF7 cells while DLG5 overexpression had opposite effects. TAZ silencing restored the sensitivity to TAM and reduced the frequency and stemness in TAM‐resistant breast cancer cells. Taken together, our data indicate that down‐regulated DLG5 expression increases the stemness of breast cancer cells by enhancing TAZ expression, contributing to TAM resistance in breast cancer. John Wiley and Sons Inc. 2018-11-18 2019-01 /pmc/articles/PMC6307757/ /pubmed/30450766 http://dx.doi.org/10.1111/jcmm.13954 Text en © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Liu, Jie
Li, Juan
Li, Pingping
Jiang, Yina
Chen, He
Wang, Ruiqi
Cao, Fang
Liu, Peijun
DLG5 suppresses breast cancer stem cell‐like characteristics to restore tamoxifen sensitivity by inhibiting TAZ expression
title DLG5 suppresses breast cancer stem cell‐like characteristics to restore tamoxifen sensitivity by inhibiting TAZ expression
title_full DLG5 suppresses breast cancer stem cell‐like characteristics to restore tamoxifen sensitivity by inhibiting TAZ expression
title_fullStr DLG5 suppresses breast cancer stem cell‐like characteristics to restore tamoxifen sensitivity by inhibiting TAZ expression
title_full_unstemmed DLG5 suppresses breast cancer stem cell‐like characteristics to restore tamoxifen sensitivity by inhibiting TAZ expression
title_short DLG5 suppresses breast cancer stem cell‐like characteristics to restore tamoxifen sensitivity by inhibiting TAZ expression
title_sort dlg5 suppresses breast cancer stem cell‐like characteristics to restore tamoxifen sensitivity by inhibiting taz expression
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307757/
https://www.ncbi.nlm.nih.gov/pubmed/30450766
http://dx.doi.org/10.1111/jcmm.13954
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