IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms7200.html
   My bibliography  Save this article

Protein kinase D1 drives pancreatic acinar cell reprogramming and progression to intraepithelial neoplasia

Author

Listed:
  • Geou-Yarh Liou

    (Mayo Clinic Comprehensive Cancer Center, Mayo Clinic)

  • Heike Döppler

    (Mayo Clinic Comprehensive Cancer Center, Mayo Clinic)

  • Ursula B. Braun

    (The Biotechnology Centre of Oslo, University of Oslo)

  • Richard Panayiotou

    (Mayo Clinic Comprehensive Cancer Center, Mayo Clinic)

  • Michele Scotti Buzhardt

    (Mayo Clinic Comprehensive Cancer Center, Mayo Clinic)

  • Derek C. Radisky

    (Mayo Clinic Comprehensive Cancer Center, Mayo Clinic)

  • Howard C. Crawford

    (Mayo Clinic Comprehensive Cancer Center, Mayo Clinic)

  • Alan P. Fields

    (Mayo Clinic Comprehensive Cancer Center, Mayo Clinic)

  • Nicole R. Murray

    (Mayo Clinic Comprehensive Cancer Center, Mayo Clinic)

  • Q. Jane Wang

    (University of Pittsburgh)

  • Michael Leitges

    (The Biotechnology Centre of Oslo, University of Oslo)

  • Peter Storz

    (Mayo Clinic Comprehensive Cancer Center, Mayo Clinic)

Abstract

The transdifferentiation of pancreatic acinar cells to a ductal phenotype (acinar-to-ductal metaplasia, ADM) occurs after injury or inflammation of the pancreas and is a reversible process. However, in the presence of activating Kras mutations or persistent epidermal growth factor receptor (EGF-R) signalling, cells that underwent ADM can progress to pancreatic intraepithelial neoplasia (PanIN) and eventually pancreatic cancer. In transgenic animal models, ADM and PanINs are initiated by high-affinity ligands for EGF-R or activating Kras mutations, but the underlying signalling mechanisms are not well understood. Here, using a conditional knockout approach, we show that protein kinase D1 (PKD1) is sufficient to drive the reprogramming process to a ductal phenotype and progression to PanINs. Moreover, using 3D explant culture of primary pancreatic acinar cells, we show that PKD1 acts downstream of TGFα and Kras, to mediate formation of ductal structures through activation of the Notch pathway.

Suggested Citation

  • Geou-Yarh Liou & Heike Döppler & Ursula B. Braun & Richard Panayiotou & Michele Scotti Buzhardt & Derek C. Radisky & Howard C. Crawford & Alan P. Fields & Nicole R. Murray & Q. Jane Wang & Michael Lei, 2015. "Protein kinase D1 drives pancreatic acinar cell reprogramming and progression to intraepithelial neoplasia," Nature Communications, Nature, vol. 6(1), pages 1-11, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7200
    DOI: 10.1038/ncomms7200
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms7200
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms7200?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. Ligia I. Bastea & Xiang Liu & Alicia K. Fleming & Veethika Pandey & Heike Döppler & Brandy H. Edenfield & Murli Krishna & Lizhi Zhang & E. Aubrey Thompson & Paul M. Grandgenett & Michael A. Hollingswo, 2024. "Coxsackievirus and adenovirus receptor expression facilitates enteroviral infections to drive the development of pancreatic cancer," Nature Communications, Nature, vol. 15(1), pages 1-11, 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:6:y:2015:i:1:d:10.1038_ncomms7200. 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.