IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v5y2014i1d10.1038_ncomms5416.html
   My bibliography  Save this article

Increased Notch signalling inhibits anoikis and stimulates proliferation of prostate luminal epithelial cells

Author

Listed:
  • Oh-Joon Kwon

    (Baylor College of Medicine)

  • Joseph M. Valdez

    (Baylor College of Medicine)

  • Li Zhang

    (Baylor College of Medicine)

  • Boyu Zhang

    (Baylor College of Medicine)

  • Xing Wei

    (Baylor College of Medicine)

  • Qingtai Su

    (Baylor College of Medicine)

  • Michael M. Ittmann

    (Baylor College of Medicine
    Dan L. Duncan Cancer Center, Baylor College of Medicine
    Michael E. DeBakey Department of Veterans Affairs Medical Center)

  • Chad J. Creighton

    (Dan L. Duncan Cancer Center, Baylor College of Medicine)

  • Li Xin

    (Baylor College of Medicine
    Baylor College of Medicine
    Dan L. Duncan Cancer Center, Baylor College of Medicine)

Abstract

The prostate epithelial lineage hierarchy remains inadequately defined. Recent lineage-tracing studies have implied the existence of prostate luminal epithelial progenitors with extensive regenerative capacity. However, this capacity has not been demonstrated in prostate stem cell activity assays, probably owing to the strong susceptibility of luminal progenitors to anoikis. Here we show that constitutive expression of Notch1 intracellular domain impairs secretory function of mouse prostate luminal cells, suppresses anoikis of luminal epithelial cells by augmenting NF-κB activity independent of Hes1, stimulates luminal cell proliferation by potentiating PI3K-AKT signalling, and rescues the capacities of the putative prostate luminal progenitors for unipotent differentiation in vivo and short-term self-renewal in vitro. Epithelial cell autonomous AR signalling is dispensable for the Notch-mediated effects. As Notch activity is increased in prostate cancers, and anoikis resistance is a hallmark for metastatic cancer cells, this study suggests a pro-metastatic function of Notch signalling during prostate cancer progression.

Suggested Citation

  • Oh-Joon Kwon & Joseph M. Valdez & Li Zhang & Boyu Zhang & Xing Wei & Qingtai Su & Michael M. Ittmann & Chad J. Creighton & Li Xin, 2014. "Increased Notch signalling inhibits anoikis and stimulates proliferation of prostate luminal epithelial cells," Nature Communications, Nature, vol. 5(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5416
    DOI: 10.1038/ncomms5416
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms5416
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms5416?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:5:y:2014:i:1:d:10.1038_ncomms5416. 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.