Notch1 induces epithelial-mesenchymal transition and the cancer stem cell phenotype in breast cancer cells and STAT3 plays a key role

Zhang,Xiaojin; Zhao,Xiaoai; Shao,Shan; Zuo,Xiaoxiao; Ning,Qian; Luo,Minna; Gu,Shanzhi; Zhao,Xinhan

doi:10.3892/ijo.2014.2809

Notch1 induces epithelial-mesenchymal transition and the cancer stem cell phenotype in breast cancer cells and STAT3 plays a key role

Authors:
- Xiaojin Zhang
- Xiaoai Zhao
- Shan Shao
- Xiaoxiao Zuo
- Qian Ning
- Minna Luo
- Shanzhi Gu
- Xinhan Zhao
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Affiliations: Department of Oncology, The First Hospital Affiliated to School of Medicine of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Respiratory, The First Hospital Affiliated to School of Medicine of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Forensic Medicine, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
Published online on: December 23, 2014 https://doi.org/10.3892/ijo.2014.2809
Pages: 1141-1148

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Abstract

Breast cancer is the most common malignancy in women. The Notch signaling pathway has been shown to be associated with the development and progression of many human cancers, including breast cancer, but the precise mechanism remains unknown. Here, the influence of Notch1 signaling in mammary epithelial cells was studied. We showed that Notch1 promotes proliferation in MCF7 and MCF10A cells. Transwell assay indicated that Notch1 overexpression promotes cell migration and the invasion of breast cancer cells. We showed that MCF7 and MCF10A cells overexpressing Notch1 acquired features of epithelial-mesenchymal transition (EMT) and displayed a cancer stem cell (CSC) phenotype. The expression levels of the epithelial markers E-cadherin and occludin were decreased, while the expression levels of the mesenchymal markers N-cadherin, vimentin and fibronectin were increased in cells overexpressing Notch1. We demonstrated that Notch1 induced phosphorylation of the signal transducer and activator of transcription 3 (STAT3) in breast cancer cells and increased the expression of p65 and interleukin (IL)-1β. Inhibition of STAT3 activity by JSI124 reduced the expression of p65 and IL-1. Treatment of MCF7-notch1 and MCF10A-notch1 cells with JSI124 also reduced the expression of N-cadherin, markers of epithelial mesenchymal transition and increased the expression of E-cadherin. Our results suggest that Notch1 promotes EMT and the CSC phenotype through induction of STAT3.

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