Heterozygous deficiency of δ-catenin impairs pathological angiogenesis

Vascular and neuronal networks share a similar branching morphology, and emerging evidence implicates common mechanisms in the formation of both systems. δ-Catenin is considered a neuronal catenin regulating neuron cell–cell adhesion and cell motility. Here, we report expression of δ-catenin in vascular endothelium, and show that deletion of only one allele of δ-catenin is sufficient to impair endothelial cell motility and vascular assembly in vitro and pathological angiogenesis in vivo, thereby inhibiting tumor growth and wound healing. In contrast, deletion of one or both allele of δ-catenin had no effects on hormone-induced physiological angiogenesis in the uterus. Molecular analysis confirmed a gene dosage effect of δ-catenin on Rho GTPase activity. Moreover, we show that inflammatory cytokines, but not angiogenic factors, regulate δ-catenin expression, and the levels of δ-catenin positively correlate to human lung cancers. Collectively, our data suggest that inflammation, commonly associated with disease conditions, induces δ-catenin expression that specifically regulates pathological, and not physiological, angiogenesis. Because only pathological angiogenesis is sensitive to decreased levels of δ-catenin, this may provide a good target for antiangiogenic therapy.