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

Silvia Batista (), Eleni Maniati, Louise E. Reynolds, Bernardo Tavora, Delphine M. Lees, Isabelle Fernandez, George Elia, Oriol Casanovas, Cristina Lo Celso, Thorsten Hagemann and Kairbaan Hodivala-Dilke ()
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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

Nature Communications, 2014, vol. 5, issue 1, 1-12

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms6054

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