DLG5 suppresses breast cancer stem cell-like characteristics to restore tamoxifen sensitivity by inhibiting TAZ expression.
Jie LiuJuan LiPingping LiYina JiangHe ChenRuiqi WangFang CaoPei-Jun LiuPublished in: Journal of cellular and molecular medicine (2018)
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.
Keyphrases
- cancer stem cells
- breast cancer cells
- poor prognosis
- estrogen receptor
- positive breast cancer
- stem cells
- epithelial mesenchymal transition
- induced apoptosis
- binding protein
- signaling pathway
- long non coding rna
- cell death
- electronic health record
- machine learning
- cell cycle arrest
- big data
- young adults
- endoplasmic reticulum stress
- combination therapy
- pi k akt