IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v5y2014i1d10.1038_ncomms6577.html
   My bibliography  Save this article

PHD3 regulates EGFR internalization and signalling in tumours

Author

Listed:
  • Boyan K. Garvalov

    (Institute of Neuropathology, University of Giessen)

  • Franziska Foss

    (Institute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences (BMLS), University of Frankfurt
    Focus Program Translational Neurosciences (FTN), University of Mainz)

  • Anne-Theres Henze

    (Institute of Neuropathology, University of Giessen
    Present addresses: Laboratory of Molecular Oncology and Angiogenesis, VRC, VIB, 3000 Leuven, Belgium)

  • Ioanna Bethani

    (Institute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences (BMLS), University of Frankfurt
    Focus Program Translational Neurosciences (FTN), University of Mainz)

  • Sabine Gräf-Höchst

    (Institute of Neuropathology, University of Giessen)

  • Devendra Singh

    (Institute of Neuropathology, University of Giessen)

  • Alina Filatova

    (Institute of Neuropathology, University of Giessen)

  • Higinio Dopeso

    (Institute of Neuropathology, University of Giessen)

  • Sascha Seidel

    (Institute of Neuropathology, University of Giessen)

  • Miriam Damm

    (Institute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences (BMLS), University of Frankfurt
    Focus Program Translational Neurosciences (FTN), University of Mainz)

  • Amparo Acker-Palmer

    (Institute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences (BMLS), University of Frankfurt
    Focus Program Translational Neurosciences (FTN), University of Mainz)

  • Till Acker

    (Institute of Neuropathology, University of Giessen)

Abstract

Tumours exploit their hypoxic microenvironment to induce a more aggressive phenotype, while curtailing the growth-inhibitory effects of hypoxia through mechanisms that are poorly understood. The prolyl hydroxylase PHD3 is regulated by hypoxia and plays an important role in tumour progression. Here we identify PHD3 as a central regulator of epidermal growth factor receptor (EGFR) activity through the control of EGFR internalization to restrain tumour growth. PHD3 controls EGFR activity by acting as a scaffolding protein that associates with the endocytic adaptor Eps15 and promotes the internalization of EGFR. In consequence, loss of PHD3 in tumour cells suppresses EGFR internalization and hyperactivates EGFR signalling to enhance cell proliferation and survival. Our findings reveal that PHD3 inactivation provides a novel route of EGFR activation to sustain proliferative signalling in the hypoxic microenvironment.

Suggested Citation

  • Boyan K. Garvalov & Franziska Foss & Anne-Theres Henze & Ioanna Bethani & Sabine Gräf-Höchst & Devendra Singh & Alina Filatova & Higinio Dopeso & Sascha Seidel & Miriam Damm & Amparo Acker-Palmer & Ti, 2014. "PHD3 regulates EGFR internalization and signalling in tumours," Nature Communications, Nature, vol. 5(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6577
    DOI: 10.1038/ncomms6577
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms6577
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms6577?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_ncomms6577. 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.