Open AccessElevated CRB 3 expression suppresses breast cancer stemness by inhibiting β‐catenin signalling to restore tamoxifen sensitivity
Author(s) -
Li Pingping,
Feng Chen,
Chen He,
Jiang Yina,
Cao Fang,
Liu Jie,
Liu Peijun
Publication year - 2018
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.13619
Subject(s) - tamoxifen , breast cancer , cancer research , cancer , catenin , biology , medicine , oncology , endocrinology , signal transduction , wnt signaling pathway , microbiology and biotechnology
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 ( CSC s) have been implicated as one of the mechanisms responsible for tamoxifen resistance. Our previous study indicated that decreased expression of the CRB 3 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 CRB 3 protein and positive for β‐catenin protein, in contrast to their matched primary tumours by immunohistochemical analysis. Furthermore, expression of CRB 3 mRNA and protein was low, while expression of β‐catenin mRNA and protein was high in tamoxifen resistance cells ( LCC 2 and T47D TamR) contrast to their corresponding cell lines MCF 7 and T47D. Similarly, CRB 3 overexpression markedly restored the tamoxifen sensitivity of TamR cells by the MTT viability assay. Finally, we found that CRB 3 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 CRB 3 is an important regulator for breast cancer stemness, which is associated with tamoxifen resistance.