Xu, JinhuaProsperi, Jenifer R.Choudhury, NouraOlopade, Olufunmilayo I.Goss, Kathleen H.2016-06-162016-06-162015-02-06Xu, J., Prosperi, J. R., Choudhury, N., Olopade, O. I., & Goss, K. H. (2015). β-Catenin Is Required for the Tumorigenic Behavior of Triple-Negative Breast Cancer Cells. PLoS ONE, 10(2), e0117097. http://doi.org/10.1371/journal.pone.0117097https://hdl.handle.net/1805/10009Our previous data illustrated that activation of the canonical Wnt signaling pathway was enriched in triple-negative breast cancer and associated with reduced overall survival in all patients. To determine whether Wnt signaling may be a promising therapeutic target for triple-negative breast cancer, we investigated whether β-catenin was necessary for tumorigenic behaviors in vivo and in vitro. β-catenin expression level was significantly reduced in two human triple-negative breast cancer cell lines, MDA-MB-231 and HCC38, using lentiviral delivery of β-catenin-specific small hairpin RNAs (shRNAs). Upon implantation of the cells in the mammary fat pad of immunocompromised mice, we found that β-catenin shRNA HCC38 cells formed markedly smaller tumors than control cells and grew much more slowly. In in vitro assays, β-catenin silencing significantly reduced the percentage of Aldefluor-positive cells, a read-out of the stem-like cell population, as well as the expression of stem cell-related target genes including Bmi-1 and c-Myc. β-catenin-knockdown cells were also significantly impaired in their ability to migrate in wound-filling assays and form anchorage-independent colonies in soft agar. β-catenin-knockdown cells were more sensitive to chemotherapeutic agents doxorubicin and cisplatin. Collectively, these data suggest that β-catenin is required for triple-negative breast cancer development by controlling numerous tumor-associated properties, such as migration, stemness, anchorage-independent growth and chemosensitivity.en-USPublisher PolicyBreastCell Line, TumorCell MovementCell ProliferationGene Expression Regulation, NeoplasticRNA InterferenceTriple Negative Breast Neoplasmsbeta CateninArticle