IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-04695-7.html
   My bibliography  Save this article

Soluble E-cadherin promotes tumor angiogenesis and localizes to exosome surface

Author

Listed:
  • Maggie K. S. Tang

    (University of Hong Kong)

  • Patrick Y. K. Yue

    (Hong Kong Baptist University)

  • Philip P. Ip

    (University of Hong Kong)

  • Rui-Lan Huang

    (Taipei Medical University)

  • Hung-Cheng Lai

    (Taipei Medical University)

  • Annie N. Y. Cheung

    (University of Hong Kong)

  • Ka Yu Tse

    (University of Hong Kong)

  • Hextan Y. S. Ngan

    (University of Hong Kong)

  • Alice S. T. Wong

    (University of Hong Kong)

Abstract

The limitations of current anti-angiogenic therapies necessitate other targets with complimentary mechanisms. Here, we show for the first time that soluble E-cadherin (sE-cad) (an 80-kDa soluble form), which is highly expressed in the malignant ascites of ovarian cancer patients, is a potent inducer of angiogenesis. In addition to ectodomain shedding, we provide further evidence that sE-cad is abundantly released in the form of exosomes. Mechanistically, sE-cad-positive exosomes heterodimerize with VE-cadherin on endothelial cells and transduce a novel sequential activation of β-catenin and NFκB signaling. In vivo and clinical data prove the relevance of sE-cad-positive exosomes for malignant ascites formation and widespread peritoneal dissemination. These data advance our understanding of the molecular regulation of angiogenesis in ovarian cancer and support the therapeutic potential of targeting sE-cad. The exosomal release of sE-cad, which represents a common route for externalization in ovarian cancer, could potentially be biomarkers for diagnosis and prognosis.

Suggested Citation

  • Maggie K. S. Tang & Patrick Y. K. Yue & Philip P. Ip & Rui-Lan Huang & Hung-Cheng Lai & Annie N. Y. Cheung & Ka Yu Tse & Hextan Y. S. Ngan & Alice S. T. Wong, 2018. "Soluble E-cadherin promotes tumor angiogenesis and localizes to exosome surface," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04695-7
    DOI: 10.1038/s41467-018-04695-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-04695-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-04695-7?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04695-7. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.