VEGFA and tumour angiogenesis

Authors

  • L. Claesson-Welsh,

    Corresponding author
    1. Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden
    • Correspondence: Lena Claesson-Welsh, Uppsala University, Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Dag Hammarskjöldsv. 20, 751 85 Uppsala, Sweden

      (fax: +46-18558931; e-mail: Lena.Welsh@igp.uu.se)

      Michael Welsh, Department of Medical Cell Biology, Uppsala University, Husargatan 3, PO Box 571, 75123 Uppsala, Sweden. (fax: +46-184714059; e-mail: michael.welsh@mcb.uu.se)

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  • M. Welsh

    Corresponding author
    1. Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
    • Correspondence: Lena Claesson-Welsh, Uppsala University, Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Dag Hammarskjöldsv. 20, 751 85 Uppsala, Sweden

      (fax: +46-18558931; e-mail: Lena.Welsh@igp.uu.se)

      Michael Welsh, Department of Medical Cell Biology, Uppsala University, Husargatan 3, PO Box 571, 75123 Uppsala, Sweden. (fax: +46-184714059; e-mail: michael.welsh@mcb.uu.se)

    Search for more papers by this author

Abstract

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.

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