IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-13852-5.html
   My bibliography  Save this article

RNF208, an estrogen-inducible E3 ligase, targets soluble Vimentin to suppress metastasis in triple-negative breast cancers

Author

Listed:
  • Kyoungwha Pang

    (Seoul National University
    CHA University)

  • Jinah Park

    (Seoul National University)

  • Sung Gwe Ahn

    (Yonsei University Medical College)

  • Jihee Lee

    (Seoul National University
    CHA University)

  • Yuna Park

    (Seoul National University
    CHA University)

  • Akira Ooshima

    (Seoul National University)

  • Seiya Mizuno

    (University of Tsukuba)

  • Satoshi Yamashita

    (National Cancer Center Research Institute)

  • Kyung-Soon Park

    (CHA University)

  • So-Young Lee

    (CHA University)

  • Joon Jeong

    (Yonsei University Medical College)

  • Toshikazu Ushijima

    (National Cancer Center Research Institute)

  • Kyung-Min Yang

    (Seoul National University)

  • Seong-Jin Kim

    (Seoul National University
    Seoul National University
    TheragenEtex Co)

Abstract

The development of triple-negative breast cancer (TNBC) negatively impacts both quality of life and survival in a high percentage of patients. Here, we show that RING finger protein 208 (RNF208) decreases the stability of soluble Vimentin protein through a polyubiquitin-mediated proteasomal degradation pathway, thereby suppressing metastasis of TNBC cells. RNF208 was significantly lower in TNBC than the luminal type, and low expression of RNF208 was strongly associated with poor clinical outcomes. Furthermore, RNF208 was induced by 17β-estradiol (E2) treatment in an estrogen receptor alpha (ΕRα)-dependent manner. Overexpression of RNF208 suppresses tumor formation and lung metastasis of TNBC cells. Mechanistically, RNF208 specifically polyubiquitinated the Lys97 residue within the head domain of Vimentin through interaction with the Ser39 residue of phosphorylated Vimentin, which exists as a soluble form, eventually facilitating proteasomal degradation of Vimentin. Collectively, our findings define RNF208 as a negative regulator of soluble Vimentin and a prognostic biomarker for TNBC cells.

Suggested Citation

  • Kyoungwha Pang & Jinah Park & Sung Gwe Ahn & Jihee Lee & Yuna Park & Akira Ooshima & Seiya Mizuno & Satoshi Yamashita & Kyung-Soon Park & So-Young Lee & Joon Jeong & Toshikazu Ushijima & Kyung-Min Yan, 2019. "RNF208, an estrogen-inducible E3 ligase, targets soluble Vimentin to suppress metastasis in triple-negative breast cancers," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13852-5
    DOI: 10.1038/s41467-019-13852-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-13852-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-13852-5?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:10:y:2019:i:1:d:10.1038_s41467-019-13852-5. 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.