Research Papers:

NUMB negatively regulates the epithelial-mesenchymal transition of triple-negative breast cancer by antagonizing Notch signaling

Jianchao Zhang, Ximing Shao, Haiyan Sun, Ke Liu, Zhihao Ding, Juntao Chen, Lijing Fang, Wu Su, Yang Hong, Huashun Li and Hongchang Li _

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Oncotarget. 2016; 7:61036-61053. https://doi.org/10.18632/oncotarget.11062

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Jianchao Zhang1, Ximing Shao1, Haiyan Sun1, Ke Liu1, Zhihao Ding1, Juntao Chen1, Lijing Fang1, Wu Su1, Yang Hong4, Huashun Li2,3, Hongchang Li1

1Shenzhen Key Laboratory for Molecular Biology of Neural Development, Guangdong Key Laboratory of Nanomedicine, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China

2SARITEX Center for Stem Cell Engineering Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine and Advanced Institute of Translational Medicine, Shanghai 200123, China

3ATCG Corporation, BioBay, Suzhou Industrial Park, Suzhou, Jiangsu 215123, China

4Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA

Correspondence to:

Hongchang Li, email: [email protected]

Huashun Li, email: [email protected]

Keywords: NUMB, EMT, TNBC, Notch, metastasis

Received: March 26, 2016     Accepted: July 19, 2016     Published: August 05, 2016


Triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer with higher rates of early relapse and metastasis, is frequently associated with aberrant activation of epithelial-mesenchymal transition (EMT). Nonetheless, how EMT is initiated and regulated during TNBC progression is not well understood. Here, we report that NUMB is a negative regulator of EMT in both human mammary epithelial cells and breast cancer cells. Reduced NUMB expression was significantly associated with elevated EMT in TNBC. Conversely, overexpression of NUMB strongly attenuated the EMT program and metastasis of TNBC cell lines. Interestingly, we showed that NUMB employs different molecular mechanisms to regulate EMT. In normal mammary epithelial cells and breast cancer cells expressing wild-type p53, NUMB suppressed EMT by stabilizing p53. However, in TNBC cells, loss of NUMB facilitated the EMT program by activating Notch signaling. Consistent with these findings, low NUMB expression and high Notch activity were significantly correlated with the TNBC subtype in patients. Collectively, these findings reveal novel molecular mechanisms of NUMB in the regulation of breast tumor EMT, especially in TNBC.

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