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

Author

Listed:
  • 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
    Ministry of Education, School of Basic Medical Sciences, Fudan University)

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.

Suggested Citation

  • Renxu Chang & Lele Song & Yi Xu & Yanjun Wu & Cheng Dai & Xinyu Wang & Xia Sun & Yingyong Hou & Wei Li & Xianbao Zhan & Lixing Zhan, 2018. "Loss of Wwox drives metastasis in triple-negative breast cancer by JAK2/STAT3 axis," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05852-8
    DOI: 10.1038/s41467-018-05852-8
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