IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v8y2017i1d10.1038_ncomms14073.html
   My bibliography  Save this article

Glucocorticoid receptor signalling activates YAP in breast cancer

Author

Listed:
  • Giovanni Sorrentino

    (Laboratorio Nazionale CIB (LNCIB), Area Science Park Padriciano)

  • Naomi Ruggeri

    (Laboratorio Nazionale CIB (LNCIB), Area Science Park Padriciano)

  • Alessandro Zannini

    (Laboratorio Nazionale CIB (LNCIB), Area Science Park Padriciano)

  • Eleonora Ingallina

    (Laboratorio Nazionale CIB (LNCIB), Area Science Park Padriciano
    Università degli Studi di Trieste)

  • Rebecca Bertolio

    (Laboratorio Nazionale CIB (LNCIB), Area Science Park Padriciano)

  • Carolina Marotta

    (Laboratorio Nazionale CIB (LNCIB), Area Science Park Padriciano)

  • Carmelo Neri

    (Laboratorio Nazionale CIB (LNCIB), Area Science Park Padriciano
    Università degli Studi di Trieste)

  • Elisa Cappuzzello

    (Oncology and Gastroenterology, University of Padova)

  • Mattia Forcato

    (University of Modena and Reggio Emilia)

  • Antonio Rosato

    (Oncology and Gastroenterology, University of Padova
    Veneto Institute of Oncology IOV-IRCCS)

  • Miguel Mano

    (Center for Neuroscience and Cell Biology (CNC), University of Coimbra
    International Centre for Genetic Engineering and Biotechnology (ICGEB))

  • Silvio Bicciato

    (University of Modena and Reggio Emilia)

  • Giannino Del Sal

    (Laboratorio Nazionale CIB (LNCIB), Area Science Park Padriciano
    Università degli Studi di Trieste)

Abstract

The Hippo pathway is an oncosuppressor signalling cascade that plays a major role in the control of cell growth, tissue homoeostasis and organ size. Dysregulation of the Hippo pathway leads to aberrant activation of the transcription co-activator YAP (Yes-associated protein) that contributes to tumorigenesis in several tissues. Here we identify glucocorticoids (GCs) as hormonal activators of YAP. Stimulation of glucocorticoid receptor (GR) leads to increase of YAP protein levels, nuclear accumulation and transcriptional activity in vitro and in vivo. Mechanistically, we find that GCs increase expression and deposition of fibronectin leading to the focal adhesion-Src pathway stimulation, cytoskeleton-dependent YAP activation and expansion of chemoresistant cancer stem cells. GR activation correlates with YAP activity in human breast cancer and predicts bad prognosis in the basal-like subtype. Our results unveil a novel mechanism of YAP activation in cancer and open the possibility to target GR to prevent cancer stem cells self-renewal and chemoresistance.

Suggested Citation

  • Giovanni Sorrentino & Naomi Ruggeri & Alessandro Zannini & Eleonora Ingallina & Rebecca Bertolio & Carolina Marotta & Carmelo Neri & Elisa Cappuzzello & Mattia Forcato & Antonio Rosato & Miguel Mano &, 2017. "Glucocorticoid receptor signalling activates YAP in breast cancer," Nature Communications, Nature, vol. 8(1), pages 1-14, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14073
    DOI: 10.1038/ncomms14073
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms14073
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms14073?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
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Camilla Tombari & Alessandro Zannini & Rebecca Bertolio & Silvia Pedretti & Matteo Audano & Luca Triboli & Valeria Cancila & Davide Vacca & Manuel Caputo & Sara Donzelli & Ilenia Segatto & Simone Vodr, 2023. "Mutant p53 sustains serine-glycine synthesis and essential amino acids intake promoting breast cancer growth," Nature Communications, Nature, vol. 14(1), pages 1-21, December.

    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:8:y:2017:i:1:d:10.1038_ncomms14073. 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.