期刊
CELLULAR SIGNALLING
卷 26, 期 3, 页码 492-501出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2013.11.023
关键词
Sox2; beta-Catenin; Breast cancer; Mass spectrometry; Transcriptional activity
类别
资金
- Canadian Institutes of Health Research
- Alberta Cancer Foundation
- CIHR Vanier Canada Graduate Scholarship
Sox2, an embryonic stem cell marker, has been recently implicated in the pathogenesis of breast cancer (BC). Using liquid chromatography-mass spectrometry and co-immunoprecipitation, we identified beta-catenin as a Sox2 binding partner in MCF7 cells. The interaction between Sox2 and beta-catenin was substantially different between the two cell subsets separated based on their differential responsiveness to a Sox2 reporter. Specifically, while beta-catenin binds to Sox2 in the nuclear fraction of cells showing reporter-responsiveness (i.e. RR cells), this interaction was not detectable in those that were reporter-unresponsive (i.e. RU cells). In RR but not in RU cells, siRNA knockdown of beta-catenin significantly upregulated the Sox2 transcriptional activity, enhanced its DNA binding and increased the expression of its target genes. Correlating with these findings, while inhibition of beta-catenin significantly downregulated the mammosphere formation efficiency in RU cells, this treatment paradoxically increased that of RR cells. To conclude, we identified that beta-catenin is an important binding partner of Sox2 and a regulator of its transcriptional activity in a small subset of BC cells. The interaction between Sox2 and beta-catenin provides a novel mechanism underlying the functional dichotomy of BC cells, which carries potential therapeutic implications. (C) 2013 Elsevier Inc All rights reserved.
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