Wnt/Frizzled signaling in angiogenesis

Abstract

The roles of growth factors such as angiopoietin (Ang) and vascular endothelial growth factor (VEGF) in angiogenesis have been known for some time, yet we have just an incipient appreciation for the contribution of Wnts to this process. Cellular proliferation and polarity, apoptosis, branching morphogenesis, inductive processes, and the maintenance of stem cells in an undifferentiated, proliferative state are all regulated by Wnt signaling. The development and maintenance of vascular structures are dependent on all these processes, and their orchestration has, to some extent, been revealed in studies of VEGF and Ang receptors. Recent evidence links the Wnt/Frizzled signaling pathway to proper vascular growth in mammals but our knowledge of Wnt function in the vasculature is rudimentary. Further insight into vascular development and the process of angiogenesis depends on evaluating the function of novel endothelial regulatory pathways such as Wnt/Frizzled signaling.

NF-κB activation in endothelial cells is critical for the activity of angiostatic agents

“…Many angiostatic agents interfere with the angiogenic process by blocking the proliferation/ survival, the migration, or the maturation of endothelial cells. The molecular targets of these agents have only been partially discovered (3,31,32). A thorough understanding of the mechanism of action of angiostatic agents, mainly at the level of proximal signaling events, is still required for the development of efficient antitumor therapies.…”

Research on WISP1 in Lung Disease

“…The WNT signaling pathway is activated via two distinct branches: the canonical and noncanonical pathways, based on the expression profiles of receptors, co-receptors, and the activity of intracellular WNT signaling regulators [50,51]. The hallmark of the canonical WNT/β-catenin pathway is that it activates the transcription factor β-catenin, a downstream effector of the pathway that is initiated by WNT ligands to form a Frizzled receptor and low density lipoprotein receptor-related protein 5/6 (LRP5/6) co-receptor complex that inactivates glycogen synthase kinase-3β (GSK3β) to block β-catenin phosphorylation and degradation that leads to accumulation of hypophosphorylated β-catenin in the cytoplasm and subsequent translocation to the nucleus, where it regulates target gene expression through interactions with a family of transcription factors [52][53][54].…”

Peptide-functionalized nanoparticles for selective targeting of pancreatic tumor

“…Since it was reported by Joyce et al [20], that the sequence CKA-K shared motifs with the Wnt-2 protein, we tested if CKAAKN could act as Wnt-2 mimetic interacting with the Frizzled (FZD) receptors, by surface plasmon resonance (SPR). Among the FZD family, we focused our attention on the FZD-5 because it has been correlated with the development of vascular abnormalities and angiogenesis processes [30,31].Since the receptor immobilization on the SPR biosensor could alter its conformation affecting the ligand binding, we chose to use the sFRP-4, a secreted frizzled-related protein with high FZD-5 sequence alignment (BLAST analysis) that was already successfully used to this aim keeping its recognition ability [32]. Interestingly, the CKAAKN peptide was able to specifically interact with the sensorchipimmobilized sFRP-4 confirming the correlation indicated previously (Supplementary material, Figure S4) [20].…”

“…The Wnt-2 belongs to a family of secreted lipid-modified signaling glycoproteins principally involved in embryonic development and tissue homeostasis [35]. Wnt-signaling pathway has also been shown to regulate the pancreatic β-cell endocrine function [36], proliferation, migration and differentiation [30]. Comprehensive genetic analysis [37][38][39] revealed that the Wnt is one of the six signaling pathways always altered in pancreatic cancers.…”