NEDD9 promotes lung cancer metastasis through epithelial–mesenchymal transition

Authors

  • Yujuan Jin,

    1. State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China
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    • Y.J., F.L. and C.Z. contributed equally to this work

  • Fei Li,

    1. State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China
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    • Y.J., F.L. and C.Z. contributed equally to this work

  • Chao Zheng,

    1. State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China
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    • Y.J., F.L. and C.Z. contributed equally to this work

  • Ye Wang,

    1. State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China
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  • Zhaoyuan Fang,

    1. State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China
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  • Chenchen Guo,

    1. State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China
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  • Xujun Wang,

    1. Department of Bioinformatics, School of Life Science and Technology, Tongji University, Shanghai, People's Republic of China
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  • Hongyan Liu,

    1. State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China
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  • Lei Deng,

    1. Department of Bioinformatics, School of Life Science and Technology, Tongji University, Shanghai, People's Republic of China
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  • Cheng Li,

    1. Department of Bioinformatics, School of Life Science and Technology, Tongji University, Shanghai, People's Republic of China
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  • Hongda Wang,

    1. State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, People's Republic of China
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  • Haiquan Chen,

    1. Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, People's Republic of China
    2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
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  • Yan Feng,

    Corresponding author
    1. State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China
    • Correspondence to: Hongbin Ji, State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, 200031 Shanghai, People's Republic of China, Tel.: +86-21-54921108, Fax: +86-21-54921101, E-mail: hbji@sibcb.ac.cn or Yan Feng, State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, 200031 Shanghai, People's Republic of China, Tel.: +86-21-54921107, Fax: +86-21-54921101, E-mail: fengyan01@sibs.ac.cn

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  • Hongbin Ji

    Corresponding author
    1. State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China
    • Correspondence to: Hongbin Ji, State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, 200031 Shanghai, People's Republic of China, Tel.: +86-21-54921108, Fax: +86-21-54921101, E-mail: hbji@sibcb.ac.cn or Yan Feng, State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, 200031 Shanghai, People's Republic of China, Tel.: +86-21-54921107, Fax: +86-21-54921101, E-mail: fengyan01@sibs.ac.cn

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Abstract

Metastasis is the major cause for high mortality of lung cancer with the underlying mechanisms poorly understood. The scaffolding protein neural precursor cell expressed, developmentally down-regulated 9 (NEDD9) has been identified as a pro-metastasis gene in several types of cancers including melanoma and breast cancer. However, the exact role and related mechanism of NEDD9 in regulating lung cancer metastasis still remain largely unknown. Here, we demonstrate that NEDD9 knockdown significantly inhibits migration, invasion and metastasis of lung cancer cells in vitro and in vivo. The pro-metastasis role of Nedd9 in lung cancer is further supported by studies in mice models of spontaneous cancer metastasis. Moreover, we find that NEDD9 promotes lung cancer cell migration and invasion through the induction of epithelial–mesenchymal transition (EMT) potentially via focal adhesion kinase activation. More importantly, NEDD9 expression inversely correlates with E-cadherin expression in human lung cancer specimens, consistent with the findings from in vitro studies. Taken together, this study highlights that NEDD9 is an important mediator promotes lung cancer metastasis via EMT.

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