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J Cell Mol Med. 2018 Jul;22(7):3423-3433. doi: 10.1111/jcmm.13619. Epub 2018 Mar 30.

Elevated CRB3 expression suppresses breast cancer stemness by inhibiting β-catenin signalling to restore tamoxifen sensitivity.

Li P1,2, Feng C3, Chen H1,2, Jiang Y4, Cao F1,2, Liu J1,2, Liu P1,2.

Author information

1
Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
2
Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
3
Department of Oncology, Shaanxi Provincial Corps Hospital, Xi'an, China.
4
Department of Pathology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Abstract

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.

KEYWORDS:

CRB3; breast cancer; cancer stem cells; tamoxifen; β-catenin

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