IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms10656.html
   My bibliography  Save this article

Lysophosphatidic acid activates Arf6 to promote the mesenchymal malignancy of renal cancer

Author

Listed:
  • Shigeru Hashimoto

    (Graduate School of Medicine, Hokkaido University)

  • Shuji Mikami

    (Keio University Hospital
    Present address: Division of Diagnostic Pathology, Keio University School of Medicine)

  • Hirokazu Sugino

    (Graduate School of Medicine, Hokkaido University)

  • Ayumu Yoshikawa

    (Graduate School of Medicine, Hokkaido University)

  • Ari Hashimoto

    (Graduate School of Medicine, Hokkaido University)

  • Yasuhito Onodera

    (Graduate School of Medicine, Hokkaido University)

  • Shotaro Furukawa

    (Graduate School of Medicine, Hokkaido University
    Graduate School of Medicine, Hokkaido University)

  • Haruka Handa

    (Graduate School of Medicine, Hokkaido University)

  • Tsukasa Oikawa

    (Graduate School of Medicine, Hokkaido University)

  • Yasunori Okada

    (Keio University School of Medicine)

  • Mototsugu Oya

    (Keio University School of Medicine)

  • Hisataka Sabe

    (Graduate School of Medicine, Hokkaido University)

Abstract

Acquisition of mesenchymal properties by cancer cells is critical for their malignant behaviour, but regulators of the mesenchymal molecular machinery and how it is activated remain elusive. Here we show that clear cell renal cell carcinomas (ccRCCs) frequently utilize the Arf6-based mesenchymal pathway to promote invasion and metastasis, similar to breast cancers. In breast cancer cells, ligand-activated receptor tyrosine kinases employ GEP100 to activate Arf6, which then recruits AMAP1; and AMAP1 then binds to the mesenchymal-specific protein EPB41L5, which promotes epithelial–mesenchymal transition and focal adhesion dynamics. In renal cancer cells, lysophosphatidic acid (LPA) activates Arf6 via its G-protein-coupled receptors, in which GTP-Gα12 binds to EFA6. The Arf6-based pathway may also contribute to drug resistance. Our results identify a specific mesenchymal molecular machinery of primary ccRCCs, which is triggered by a product of autotaxin and it is associated with poor outcome of patients.

Suggested Citation

  • Shigeru Hashimoto & Shuji Mikami & Hirokazu Sugino & Ayumu Yoshikawa & Ari Hashimoto & Yasuhito Onodera & Shotaro Furukawa & Haruka Handa & Tsukasa Oikawa & Yasunori Okada & Mototsugu Oya & Hisataka S, 2016. "Lysophosphatidic acid activates Arf6 to promote the mesenchymal malignancy of renal cancer," Nature Communications, Nature, vol. 7(1), pages 1-11, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10656
    DOI: 10.1038/ncomms10656
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms10656
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms10656?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:7:y:2016:i:1:d:10.1038_ncomms10656. 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.