Loss of Wwox drives metastasis in triple-negative breast cancer by JAK2/STAT3 axis

Renxu Chang, Lele Song, Yi Xu, Yanjun Wu, Cheng Dai, Xinyu Wang, Xia Sun, Yingyong Hou, Wei Li, Xianbao Zhan and Lixing Zhan ()
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Renxu Chang: University of the Chinese Academy of Sciences
Lele Song: University of the Chinese Academy of Sciences
Yi Xu: University of the Chinese Academy of Sciences
Yanjun Wu: University of the Chinese Academy of Sciences
Cheng Dai: University of the Chinese Academy of Sciences
Xinyu Wang: University of the Chinese Academy of Sciences
Xia Sun: University of the Chinese Academy of Sciences
Yingyong Hou: Fudan University
Wei Li: Zhejiang University
Xianbao Zhan: Second Military Medical University
Lixing Zhan: University of the Chinese Academy of Sciences

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract Loss of WW domain-containing oxidoreductase (Wwox) expression has been observed in breast cancer (BC). However, its regulatory effects are largely unknown, especially in triple-negative breast cancer (TNBC). Herein, gene expression profiling revealed that JAK/STAT3 pathway was one of the most differentially modulated pathways in basal-like BC cells. The lower expression of Wwox was significantly correlated with high activation of STAT3 in basal-like cells and TNBC tissues. Overexpression of Wwox markedly inhibited proliferation and metastasis of BC cells by suppressing STAT3 activation, which is to interact with JAK2 to inhibit JAK2 and STAT3 phosphorylation. Furthermore, Wwox limited STAT3 binding to the interleukin-6 promoter, repressing expression of the IL-6 cytokine. Altogether, our data established that Wwox suppresses BC cell metastasis and proliferation by JAK2/STAT3 pathway. Targeting of Wwox with STAT3 could offer a promising therapeutic strategy for TNBC.

Date: 2018
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DOI: 10.1038/s41467-018-05852-8

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