Wnt Signaling in Angiogenesis

Abstract

Although progress has been made in understanding the role of growth factors and their receptors in angiogenesis, little is known about how the Wnt family of growth factors function in the vasculature. Wnts are multifunctional factors that act through the frizzled receptors to regulate proliferation, apoptosis, branching morphogenesis, inductive processes, and cell polarity. All of these processes must occur as developing vascular structures are formed and maintained. Recent evidence has linked the Wnt/Frizzled signaling pathway to proper vascular growth in murine and human retina. Here we review the literature describing the angiogenic functions for Wnt signaling and focus on a newly discovered angiogenic factor, Norrin, which acts through the Wnt receptor, Frizzled4.

Angiogenesis and clinicopathologic characteristics in different hepatocellular carcinoma subtypes defined by EpCAM and α-fetoprotein expression status

“…HCC [2]. Recent evidences suggest that Wnt/b-catenin signaling also plays a pivotal role in inducing angiogenesis [14,15]. Wnt/b-catenin pathway appears to target genes encoding angiogenic regulators such as VEGF-A [16,17].…”

Wnt Signaling in Mammary Glands: Plastic Cell Fates and Combinatorial Signaling

“…For example, endothelial cell maturation is highly Wnt dependent (Parmalee and Kitajewski 2008), including a relatively little characterized pathway that depends on the Norrin ligand and Fzd4/Lrp5 (Ye et al 2010). Macrophages and other immunomodulatory cells are well known to affect mammary development, involution, and tumor progression (Schwertfeger et al 2006;Schaale et al 2011;O'Brien et al 2012).…”

Lipid Phosphate Phosphatase 3 Stabilization of β-Catenin Induces Endothelial Cell Migration and Formation of Branching Point Structures

“…To further test the hypothesis that LPP3 stimulates LEF-1 activation, we determined the expression of the specific LEF-1 target gene, fibronectin (26,27). Expression of fibronectin is known to mediate EC adhesion, migration, proliferation, and cellular polarity (29)(30)(31)(32)(33)(34). Thus, we performed an ELISA to measure the production of fibronectin as well as a non-LEF-1-regulated protein, tissue inhibitor of metalloproteinases 2 (TIMP-2), in supernatants of 50% subconfluent EC cultures.…”

“…The VE-cadherin cytoplasmic domain interacts with the Armadillo domain-containing proteins, ␤-catenin, ␥-catenin (plakoglobin), and p120-catenin (p120ctn) (2,15,38,40,43). Genetic and biochemical evidence documents a crucial role of ␤-catenin in regulating cell adhesion as well as proliferation secondary to the central position of ␤-catenin in the Wnt signaling pathway (13,16,25,31,44). In addition, the juxtamembrane protein p120ctn regulates AJ stability via binding to VE-cadherin (2,7,9,15,21,28,32,43).…”