Open AccessDLG 5 suppresses breast cancer stem cell‐like characteristics to restore tamoxifen sensitivity by inhibiting TAZ expression
Author(s) -
Liu Jie,
Li Juan,
Li Pingping,
Jiang Yina,
Chen He,
Wang Ruiqi,
Cao Fang,
Liu Peijun
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13954
Subject(s) - tamoxifen , breast cancer , estrogen receptor , cancer research , gene silencing , cancer , cancer stem cell , cancer cell , mcf 7 , biology , medicine , human breast , biochemistry , gene
Abstract 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 ( DLG 5) expression is down‐regulated in TAM ‐resistant breast cancer and cells. DLG 5 silencing decreased the sensitivity to TAM and increased the frequency and stemness of CD 44 + / CD 24 − breast cancer stem cells ( BCSC s) and TAZ , a transducer of the Hippo pathway, expression in MCF 7 cells while DLG 5 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 DLG 5 expression increases the stemness of breast cancer cells by enhancing TAZ expression, contributing to TAM resistance in breast cancer.