Elevated CRB3 expression suppresses breast cancer stemness by inhibiting β-catenin signalling to restore tamoxifen sensitivity.
Elevated CRB3 expression suppresses breast cancer stemness by inhibiting β-catenin signalling to restore tamoxifen sensitivity.
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CRB3 表达升高通过抑制 β-连环蛋白信号传导来恢复他莫昔芬敏感性，从而抑制乳腺癌干性
DOI：
10.1111/jcmm.13619
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发表时间：
2018-07
影响因子：
5.3
通讯作者：
Liu P
中科院分区：
文献类型：
--
作者：
Li P;Feng C;Chen H;Jiang Y;Cao F;Liu J;Liu P
他莫昔芬是雌激素受体阳性乳腺癌患者激素治疗（HT）的一线药物。然而，其中 20% 至 30% 的患者对他莫昔芬治疗有耐药性。癌症干细胞（CSC）被认为是导致他莫昔芬耐药的机制之一。我们之前的研究表明，CRB3 基因表达的减少赋予乳腺癌细胞干细胞特征。在目前的研究中，我们通过免疫组织化学分析发现，大多数对他莫昔芬耐药的乳腺癌患者组织的CRB3蛋白呈阴性，而β-catenin蛋白呈阳性，这与其匹配的原发肿瘤相反。此外，与相应的细胞系 MCF7 和 T47D 相比，他莫昔芬耐药细胞（LCC2 和 T47D TamR）中 CRB3 mRNA 和蛋白的表达较低，而 β-catenin mRNA 和蛋白的表达较高。同样，通过 MTT 活力测定，CRB3 过表达显着恢复了 TamR 细胞对他莫昔芬的敏感性。最后，我们发现CRB3通过抑制β-连环蛋白信号传导来抑制TamR细胞的干性，这可能反过来导致乳腺癌细胞群的减少。此外，这些发现表明 CRB3 是乳腺癌干性的重要调节因子，与他莫昔芬耐药性相关。
Tamoxifen is a first‐line drug for hormone therapy (HT) in oestrogen receptor‐positive breast cancer patients. However, 20% to 30% of those patients are resistant to tamoxifen treatment. Cancer stem cells (CSCs) have been implicated as one of the mechanisms responsible for tamoxifen resistance. Our previous study indicated that decreased expression of the CRB3 gene confers stem cell characteristics to breast cancer cells. In the current investigation, we found that most of the breast cancer patient tissues resistant to tamoxifen were negative for CRB3 protein and positive for β‐catenin protein, in contrast to their matched primary tumours by immunohistochemical analysis. Furthermore, expression of CRB3 mRNA and protein was low, while expression of β‐catenin mRNA and protein was high in tamoxifen resistance cells (LCC2 and T47D TamR) contrast to their corresponding cell lines MCF7 and T47D. Similarly, CRB3 overexpression markedly restored the tamoxifen sensitivity of TamR cells by the MTT viability assay. Finally, we found that CRB3 suppressed the stemness of TamR cells by inhibiting β‐catenin signalling, which may in turn lead to a decrease in the breast cancer cell population. Furthermore, these findings indicate that CRB3 is an important regulator for breast cancer stemness, which is associated with tamoxifen resistance.
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DOI：
10.1186/bcr3609
发表时间：
2014-01-29
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Kazi AA;Gilani RA;Schech AJ;Chumsri S;Sabnis G;Shah P;Goloubeva O;Kronsberg S;Brodie AH
通讯作者：
Brodie AH
影响因子：
3.7
作者：
Liu H;Wang G;Yang L;Qu J;Yang Z;Zhou X
通讯作者：
Zhou X
影响因子：
254.7
作者：
Siegel, Rebecca;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
DOI：
10.1083/jcb.200609096
发表时间：
2007-07-30
期刊：
The Journal of cell biology
影响因子：
--
作者：
Fan S;Fogg V;Wang Q;Chen XW;Liu CJ;Margolis B
通讯作者：
Margolis B
影响因子：
11.8
作者：
Varelas, Xaralabos;Samavarchi-Tehrani, Payman;Wrana, Jeffrey L.
通讯作者：
Wrana, Jeffrey L.