IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v4y2013i1d10.1038_ncomms3443.html
   My bibliography  Save this article

Targeting BIG3–PHB2 interaction to overcome tamoxifen resistance in breast cancer cells

Author

Listed:
  • Tetsuro Yoshimaru

    (Institute for Genome Research, The University of Tokushima)

  • Masato Komatsu

    (Institute for Genome Research, The University of Tokushima)

  • Taisuke Matsuo

    (Institute for Genome Research, The University of Tokushima)

  • Yi-An Chen

    (National Institute of Biomedical Innovation)

  • Yoichi Murakami

    (National Institute of Biomedical Innovation
    Present address: Graduate School of Information Sciences, Tohoku University, 6-3-09, Aramaki-aza-aoba, Aoba-ku, Sendai-city, Miyagi 980-8579, Japan)

  • Kenji Mizuguchi

    (National Institute of Biomedical Innovation)

  • Eiichi Mizohata

    (Graduate School of Engineering, Osaka University)

  • Tsuyoshi Inoue

    (Graduate School of Engineering, Osaka University)

  • Miki Akiyama

    (Laboratory of Molecular Medicine, University of Tokyo)

  • Rui Yamaguchi

    (Laboratory of Sequence Analysis, The University of Tokyo)

  • Seiya Imoto

    (Laboratory of DNA Information Analysis, Human Genome Centre, Institute of Medical Science, The University of Tokyo)

  • Satoru Miyano

    (Laboratory of DNA Information Analysis, Human Genome Centre, Institute of Medical Science, The University of Tokyo)

  • Yasuo Miyoshi

    (Hyogo College of Medicine)

  • Mitsunori Sasa

    (Tokushima Breast Care Clinic)

  • Yusuke Nakamura

    (Laboratory of Molecular Medicine, University of Tokyo
    The University of Chicago)

  • Toyomasa Katagiri

    (Institute for Genome Research, The University of Tokushima)

Abstract

The acquisition of endocrine resistance is a common obstacle in endocrine therapy of patients with oestrogen receptor-α (ERα)-positive breast tumours. We previously demonstrated that the BIG3–PHB2 complex has a crucial role in the modulation of oestrogen/ERα signalling in breast cancer cells. Here we report a cell-permeable peptide inhibitor, called ERAP, that regulates multiple ERα-signalling pathways associated with tamoxifen resistance in breast cancer cells by inhibiting the interaction between BIG3 and PHB2. Intrinsic PHB2 released from BIG3 by ERAP directly binds to both nuclear- and membrane-associated ERα, which leads to the inhibition of multiple ERα-signalling pathways, including genomic and non-genomic ERα activation and ERα phosphorylation, and the growth of ERα-positive breast cancer cells both in vitro and in vivo. More importantly, ERAP treatment suppresses tamoxifen resistance and enhances tamoxifen responsiveness in ERα-positive breast cancer cells. These findings suggest inhibiting the interaction between BIG3 and PHB2 may be a new therapeutic strategy for the treatment of luminal-type breast cancer.

Suggested Citation

  • Tetsuro Yoshimaru & Masato Komatsu & Taisuke Matsuo & Yi-An Chen & Yoichi Murakami & Kenji Mizuguchi & Eiichi Mizohata & Tsuyoshi Inoue & Miki Akiyama & Rui Yamaguchi & Seiya Imoto & Satoru Miyano & Y, 2013. "Targeting BIG3–PHB2 interaction to overcome tamoxifen resistance in breast cancer cells," Nature Communications, Nature, vol. 4(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3443
    DOI: 10.1038/ncomms3443
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms3443
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms3443?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:4:y:2013:i:1:d:10.1038_ncomms3443. 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.