IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v5y2014i1d10.1038_ncomms6054.html
   My bibliography  Save this article

Haematopoietic focal adhesion kinase deficiency alters haematopoietic homeostasis to drive tumour metastasis

Author

Listed:
  • Silvia Batista

    (Centre for Tumour Biology, Barts Cancer Institute—a Cancer Research UK Centre of Excellence, Queen Mary, University of London, John Vane Science Centre, Charterhouse Square)

  • Eleni Maniati

    (Centre for Cancer and Inflammation, Barts Cancer Institute—a Cancer Research UK Centre of Excellence, Queen Mary, University of London, John Vane Science Centre, Charterhouse Square)

  • Louise E. Reynolds

    (Centre for Tumour Biology, Barts Cancer Institute—a Cancer Research UK Centre of Excellence, Queen Mary, University of London, John Vane Science Centre, Charterhouse Square)

  • Bernardo Tavora

    (Centre for Tumour Biology, Barts Cancer Institute—a Cancer Research UK Centre of Excellence, Queen Mary, University of London, John Vane Science Centre, Charterhouse Square)

  • Delphine M. Lees

    (Centre for Tumour Biology, Barts Cancer Institute—a Cancer Research UK Centre of Excellence, Queen Mary, University of London, John Vane Science Centre, Charterhouse Square)

  • Isabelle Fernandez

    (Centre for Tumour Biology, Barts Cancer Institute—a Cancer Research UK Centre of Excellence, Queen Mary, University of London, John Vane Science Centre, Charterhouse Square)

  • George Elia

    (Centre for Tumour Biology, Barts Cancer Institute—a Cancer Research UK Centre of Excellence, Queen Mary, University of London, John Vane Science Centre, Charterhouse Square)

  • Oriol Casanovas

    (Translational Research Laboratory, Catalan Institute of Oncology, IDIBELL)

  • Cristina Lo Celso

    (Sir Alexander Fleming building, Imperial College)

  • Thorsten Hagemann

    (Centre for Cancer and Inflammation, Barts Cancer Institute—a Cancer Research UK Centre of Excellence, Queen Mary, University of London, John Vane Science Centre, Charterhouse Square)

  • Kairbaan Hodivala-Dilke

    (Centre for Tumour Biology, Barts Cancer Institute—a Cancer Research UK Centre of Excellence, Queen Mary, University of London, John Vane Science Centre, Charterhouse Square)

Abstract

Metastasis is the main cause of cancer-related death and thus understanding the molecular and cellular mechanisms underlying this process is critical. Here, our data demonstrate, contrary to established dogma, that loss of haematopoietic-derived focal adhesion kinase (FAK) is sufficient to enhance tumour metastasis. Using both experimental and spontaneous metastasis models, we show that genetic ablation of haematopoietic FAK does not affect primary tumour growth but enhances the incidence of metastasis significantly. At a molecular level, haematopoietic FAK deletion results in an increase in PU-1 levels and decrease in GATA-1 levels causing a shift of hematopoietic homeostasis towards a myeloid commitment. The subsequent increase in circulating granulocyte number, with an increase in serum CXCL12 and granulocyte CXCR4 levels, was required for augmented metastasis in mice lacking haematopoietic FAK. Overall our findings provide a mechanism by which haematopoietic FAK controls cancer metastasis.

Suggested Citation

  • Silvia Batista & Eleni Maniati & Louise E. Reynolds & Bernardo Tavora & Delphine M. Lees & Isabelle Fernandez & George Elia & Oriol Casanovas & Cristina Lo Celso & Thorsten Hagemann & Kairbaan Hodival, 2014. "Haematopoietic focal adhesion kinase deficiency alters haematopoietic homeostasis to drive tumour metastasis," Nature Communications, Nature, vol. 5(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6054
    DOI: 10.1038/ncomms6054
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms6054
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms6054?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_ncomms6054. 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.