IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-13091-8.html
   My bibliography  Save this article

A gene regulatory network to control EMT programs in development and disease

Author

Listed:
  • Hassan Fazilaty

    (Avda. Ramón y Cajal s/n, Sant Joan d’
    University of Zurich)

  • Luciano Rago

    (Avda. Ramón y Cajal s/n, Sant Joan d’
    Academic Medical Center)

  • Khalil Kass Youssef

    (Avda. Ramón y Cajal s/n, Sant Joan d’)

  • Oscar H. Ocaña

    (Avda. Ramón y Cajal s/n, Sant Joan d’)

  • Francisco Garcia-Asencio

    (Avda. Ramón y Cajal s/n, Sant Joan d’)

  • Aida Arcas

    (Avda. Ramón y Cajal s/n, Sant Joan d’
    University of Navarra)

  • Juan Galceran

    (Avda. Ramón y Cajal s/n, Sant Joan d’)

  • M. Angela Nieto

    (Avda. Ramón y Cajal s/n, Sant Joan d’)

Abstract

The Epithelial to Mesenchymal Transition (EMT) regulates cell plasticity during embryonic development and in disease. It is dynamically orchestrated by transcription factors (EMT-TFs), including Snail, Zeb, Twist and Prrx, all activated by TGF-β among other signals. Here we find that Snail1 and Prrx1, which respectively associate with gain or loss of stem-like properties and with bad or good prognosis in cancer patients, are expressed in complementary patterns during vertebrate development and in cancer. We show that this complementarity is established through a feedback loop in which Snail1 directly represses Prrx1, and Prrx1, through direct activation of the miR-15 family, attenuates the expression of Snail1. We also describe how this gene regulatory network can establish a hierarchical temporal expression of Snail1 and Prrx1 during EMT and validate its existence in vitro and in vivo, providing a mechanism to switch and select different EMT programs with important implications in development and disease.

Suggested Citation

  • Hassan Fazilaty & Luciano Rago & Khalil Kass Youssef & Oscar H. Ocaña & Francisco Garcia-Asencio & Aida Arcas & Juan Galceran & M. Angela Nieto, 2019. "A gene regulatory network to control EMT programs in development and disease," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13091-8
    DOI: 10.1038/s41467-019-13091-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-13091-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-13091-8?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_s41467-019-13091-8. 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.