VEGFA and tumour angiogenesis

被引:762
作者
Claesson-Welsh, L. [1 ]
Welsh, M. [2 ]
机构
[1] Uppsala Univ, Dept Immunol Genet & Pathol, Rudbeck Lab, S-75185 Uppsala, Sweden
[2] Uppsala Univ, Dept Med Cell Biol, S-75123 Uppsala, Sweden
基金
瑞典研究理事会;
关键词
angiogenesis; signal transduction; tumours; vascular permeability; VEGFA; VEGFR2; ENDOTHELIAL-GROWTH-FACTOR; FOCAL ADHESION KINASE; NITRIC-OXIDE SYNTHASE; ACTIVATED PROTEIN-KINASE; A-DEPENDENT ACTIVATION; FACTOR RECEPTOR KDR; ADAPTER PROTEIN; VASCULAR-PERMEABILITY; VE-CADHERIN; CELL MIGRATION;
D O I
10.1111/joim.12019
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Claesson-Welsh L, Welsh M (Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden and Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden). VEGFA and tumour angiogenesis (Review). J Intern Med 2013; 273: 114-127. In this review we summarize the current understanding of signal transduction downstream of vascular endothelial growth factor A (VEGFA) and its receptor VEGFR2, and the relationship between these signal transduction pathways and the hallmark responses of VEGFA, angiogenesis and vascular permeability. These physiological responses involve a number of effectors, including extracellular signal-regulated kinases (ERKs), Src, phosphoinositide 3 kinase (PI3K)/Akt, focal adhesion kinase (FAK), Rho family GTPases, endothelial NO and p38 mitogen-activated protein kinase (MAPK). Several of these factors are involved in the regulation of both angiogenesis and vascular permeability. Tumour angiogenesis primarily relies on VEGFA-driven responses, which to a large extent result in a dysfunctional vasculature. The reason for this remains unclear, although it appears that certain aspects of the VEGFA-stimulated angiogenic milieu (high level of microvascular density and permeability) promote tumour expansion. The high degree of redundancy and complexity of VEGFA-driven tumour angiogenesis may explain why tumours commonly develop resistance to anti-angiogenic therapy targeting VEGFA signal transduction.
引用
收藏
页码:114 / 127
页数:14
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