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Molecular & Cellular Proteomics

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Research

Cancer cell derived small extracellular vesicles contribute to recipient cell metastasis through promoting HGF/c-Met pathway

Zhi Qiao, Yan Zhang, Maolin Ge, Sha Liu, Xiaoteng Jiang, Zhi Shang, View ORCID ProfileHan Liu, Chengxi Cao and View ORCID ProfileHua Xiao  Correspondence email
Molecular & Cellular Proteomics June 13, 2019, mcp.RA119.001502; https://doi.org/10.1074/mcp.RA119.001502
Zhi Qiao
Shanghai Jiao Tong University, China
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Yan Zhang
Shanghai Jiao Tong University, China
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Maolin Ge
Shanghai Jiao Tong University, China
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Sha Liu
Shanghai Jiao Tong University, China
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Xiaoteng Jiang
Shanghai Jiao Tong University, China
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Zhi Shang
Shanghai Jiao Tong University, China
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Han Liu
Shanghai Jiao Tong University, China
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  • ORCID record for Han Liu
Chengxi Cao
Shanghai Jiao Tong University
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Hua Xiao
Shanghai Jiao Tong University, China
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  • For correspondence: xiaohuacn@gmail.com
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Abstract

Cancer progression is frequently caused by metastasis and leads to significantly increased mortality. Cell derived extracellular vesicles, including exosomes, in the microenvironment play key roles in cellular signal transduction, while their biological function in cancer metastasis and progression needs in-depth investigation. Here, we initially demonstrate that the small extracellular vesicles (sEVs) derived from highly metastatic lung cancer cells exhibited great capacity to promote the progression of recipient cells. Quantitative proteomics was employed to comprehensively decipher the proteome of cell derived sEVs and more than 1400 sEVs proteins were identified. Comparison analysis indicates that sEVs-HGF is a potential metastasis related protein and our verification data from clinical lung cancer plasma samples and in vivo experiments further confirmed the association. We found that sEVs-HGF could induce epithelial-mesenchymal transition and the coordination between HGF and c-Met was confirmed through corresponding target knockdown and kinase inhibition. Our data collectively demonstrate that cancer cell derived sEVs contribute to recipient cell metastasis through promoting HGF/c-Met pathway, which are potential targets for the prevention and treatment of cancer metastasis.

  • Proteomics
  • HGF/c-Met pathway
  • Exosomes
  • Lung cancer
  • Mass Spectrometry
  • Metastasis
  • Subcellular analysis

Footnotes

  • Author contributions: Z.Q., Y.Z., M.G., and H.X. designed research; Z.Q., Y.Z., M.G., and H.X. performed research; Z.Q., Y.Z., M.G., and H.X. contributed new reagents/analytic tools; Z.Q., Y.Z., M.G., S.L., X.J., Z.S., H.L., C.C., and H.X. analyzed data; Z.Q., Y.Z., M.G., and H.X. wrote the paper.

  • Received May 3, 2019.
  • Revision received June 11, 2019.
  • Accepted June 13, 2019.
  • Published under license by The American Society for Biochemistry and Molecular Biology, Inc.
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Cancer cell derived small extracellular vesicles contribute to recipient cell metastasis through promoting HGF/c-Met pathway
Zhi Qiao, Yan Zhang, Maolin Ge, Sha Liu, Xiaoteng Jiang, Zhi Shang, Han Liu, Chengxi Cao, Hua Xiao
Molecular & Cellular Proteomics June 13, 2019, mcp.RA119.001502; DOI: 10.1074/mcp.RA119.001502

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Cancer cell derived small extracellular vesicles contribute to recipient cell metastasis through promoting HGF/c-Met pathway
Zhi Qiao, Yan Zhang, Maolin Ge, Sha Liu, Xiaoteng Jiang, Zhi Shang, Han Liu, Chengxi Cao, Hua Xiao
Molecular & Cellular Proteomics June 13, 2019, mcp.RA119.001502; DOI: 10.1074/mcp.RA119.001502
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