期刊
NATURE COMMUNICATIONS
卷 5, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms6054
关键词
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资金
- Cancer Research UK [C82181/A12007, C18270/A12888, C18270/A14355]
- Breast Cancer Campaign [2010MayPR39]
- Association of International Cancer Research [12-1068]
- Medical Research Council [G0901609]
- Pancreatic Cancer Research Fund
- People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme FP7 under REA grant agreement [317445]
- Biotechnology and Biological Sciences Research Council [BB/K021168/1, BB/I004033/1] Funding Source: researchfish
- Cancer Research UK [11831, 12007] Funding Source: researchfish
- Medical Research Council [G0901609] Funding Source: researchfish
- Worldwide Cancer Research [12-1068] Funding Source: researchfish
- BBSRC [BB/I004033/1, BB/K021168/1] Funding Source: UKRI
- MRC [G0901609] Funding Source: UKRI
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.
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