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

DLG5 suppresses breast cancer stem cell-like characteristics to restore tamoxifen sensitivity by inhibiting TAZ expression.
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DLG5 抑制乳腺癌干细胞样特征,通过抑制 TAZ 表达来恢复他莫昔芬敏感性

DOI:
10.1111/jcmm.13954
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发表时间:
2019-01
影响因子:
5.3
通讯作者:
Liu P
Liu P
中科院分区:
医学2区
文献类型:
--
作者:
Liu J;Li J;Li P;Jiang Y;Chen H;Wang R;Cao F;Liu P

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他莫昔芬(TAM)是治疗雌激素受体阳性乳腺癌的主要药物。然而,TAM耐药仍然是乳腺癌患者的严重威胁,可能归因于乳腺癌的干性增加。在这里,我们表明,磁盘大同源物5(DLG 5)表达下调TAM耐药乳腺癌和细胞。DLG 5沉默降低了对TAM的敏感性,并增加了CD 44 +/CD 24 −乳腺癌干细胞(BCSC)和TAZ(Hippo通路的转导子)在MCF 7细胞中表达的频率和干性,而DLG 5过表达具有相反的效果。TAZ沉默恢复了对TAM的敏感性,并降低了TAM耐药乳腺癌细胞的频率和干性。总之,我们的数据表明,下调的DLG 5表达通过增强TAZ表达增加乳腺癌细胞的干细胞性,有助于乳腺癌中的TAM耐药性。
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.
DLG5 缺失通过抑制 Hippo 信号通路促进乳腺癌恶性
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