Pericyte FAK negatively regulates Gas6/Axl signalling to suppress tumour angiogenesis and tumour growth.
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The overexpression of the protein tyrosine kinase, Focal adhesion kinase (FAK), in endothelial cells has implicated its requirement in angiogenesis and tumour growth, but how pericyte FAK regulates tumour angiogenesis is unknown. We show that pericyte FAK regulates tumour growth and angiogenesis in multiple mouse models of melanoma, lung carcinoma and pancreatic B-cell insulinoma and provide evidence that loss of pericyte FAK enhances Gas6-stimulated phosphorylation of the receptor tyrosine kinase, Axl with an upregulation of Cyr61, driving enhanced tumour growth. We further show that pericyte derived Cyr61 instructs tumour cells to elevate expression of the proangiogenic/protumourigenic transmembrane receptor Tissue Factor. Finally, in human melanoma we show that when 50% or more tumour blood vessels are pericyte-FAK negative, melanoma patients are stratified into those with increased tumour size, enhanced blood vessel density and metastasis. Overall our data uncover a previously unknown mechanism of tumour growth by pericytes that is controlled by pericyte FAK.
Mice, Inbred C57BL
Carcinoma, Lewis Lung
Receptor Protein-Tyrosine Kinases
Intercellular Signaling Peptides and Proteins
Vascular Endothelial Growth Factor A
Platelet-Derived Growth Factor
Proto-Oncogene Proteins c-sis
Gene Expression Regulation, Neoplastic
Focal Adhesion Kinase 1
Cysteine-Rich Protein 61
Placenta Growth Factor
Cell Death and Immunity
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Nature communications, 2020, 11 (1), pp. 2810 - ?
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0
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