Endothelial FAK is required for tumour angiogenesis

作者: Bernardo Tavora , Silvia Batista , Louise E. Reynolds , Shalini Jadeja , Stephen Robinson

DOI: 10.1002/EMMM.201000106

关键词:

摘要: Focal adhesion kinase (FAK) is a cytoplasmic tyrosine that plays fundamental role in integrin and growth factor mediated signalling an important player cell migration proliferation, processes vital for angiogenesis. However, the of FAK adult pathological angiogenesis unknown. We have generated endothelial-specific tamoxifen-inducible knockout mice by crossing FAK-floxed (FAKfl/fl) with platelet derived b (Pdgfb)-iCreER mice. Tamoxifen-treatment Pdgfb-iCreER;FAKfl/fl results deletion endothelial cells (ECs) without any adverse effects. Importantly however, FAK-deletion inhibited tumour reduced Furthermore, vivo angiogenic assays impairs vascular (VEGF)-induced neovascularization. In addition, vitro ECs resulted VEGF-stimulated Akt phosphorylation correlating cellular proliferation as well increased death. Our data suggest required validates possible target anti-angiogenic therapies.

参考文章(46)
Platelets and angiogenesis in malignancy. Seminars in Thrombosis and Hemostasis. ,vol. 30, pp. 95- 108 ,(2004) , 10.1055/S-2004-822974
Louise E. Reynolds, Kairbaan M. Hodivala-Dilke, Primary mouse endothelial cell culture for assays of angiogenesis. Methods in molecular medicine. ,vol. 120, pp. 503- 509 ,(2006) , 10.1385/1-59259-969-9:503
M. C. Puri, J. Rossant, K. Alitalo, A. Bernstein, J. Partanen, THE RECEPTOR TYROSINE KINASE TIE IS REQUIRED FOR INTEGRITY AND SURVIVAL OF VASCULAR ENDOTHELIAL-CELLS The EMBO Journal. ,vol. 14, pp. 5884- 5891 ,(1995) , 10.1002/J.1460-2075.1995.TB00276.X
Veronica Gabarra-Niecko, FAK regulates biological processes important for the pathogenesis of cancer. Cancer and Metastasis Reviews. ,vol. 22, pp. 359- 374 ,(2003) , 10.1023/A:1023725029589
Louise E. Reynolds, Lorenza Wyder, Julie C. Lively, Daniela Taverna, Stephen D. Robinson, Xiaozhu Huang, Dean Sheppard, Richard O. Hynes, Kairbaan M. Hodivala-Dilke, Enhanced Pathological Angiogenesis in Mice Lacking beta3 Integrin or beta3 and beta5 Integrins Nature Medicine. ,vol. 8, pp. 27- 34 ,(2002) , 10.1038/NM0102-27
George D. Yancopoulos, Samuel Davis, Nicholas W. Gale, John S. Rudge, Stanley J. Wiegand, Jocelyn Holash, Vascular-specific growth factors and blood vessel formation Nature. ,vol. 407, pp. 242- 248 ,(2000) , 10.1038/35025215
Rita Silva, Gabriela D'Amico, Kairbaan M. Hodivala-Dilke, Louise E. Reynolds, Integrins: The Keys to Unlocking Angiogenesis Arteriosclerosis, Thrombosis, and Vascular Biology. ,vol. 28, pp. 1703- 1713 ,(2008) , 10.1161/ATVBAHA.108.172015
Satyajit K Mitra, David D Schlaepfer, Integrin-regulated FAK-Src signaling in normal and cancer cells. Current Opinion in Cell Biology. ,vol. 18, pp. 516- 523 ,(2006) , 10.1016/J.CEB.2006.08.011
Juhua Chen, Payaningal R Somanath, Olga Razorenova, William S Chen, Nissim Hay, Paul Bornstein, Tatiana V Byzova, None, Akt1 regulates pathological angiogenesis, vascular maturation and permeability in vivo Nature Medicine. ,vol. 11, pp. 1188- 1196 ,(2005) , 10.1038/NM1307
S K Mitra, D Mikolon, J E Molina, D A Hsia, D A Hanson, A Chi, S-T Lim, J A Bernard-Trifilo, D Ilic, D G Stupack, D A Cheresh, D D Schlaepfer, Intrinsic FAK activity and Y925 phosphorylation facilitate an angiogenic switch in tumors. Oncogene. ,vol. 25, pp. 5969- 5984 ,(2006) , 10.1038/SJ.ONC.1209588