Untangling the signaling pathways involved in endothelial cell biology is of central interest for the development of antiangiogenesis based therapies. Here we report that Wnt3a induces the proliferation and migration of HUVECs, but does not affect their Survival. Wnt3a-induced proliferation was VEGFR signaling independent, but reduced upon CamKII inhibition. In a search for the downstream mediators of Wnt3a's effects oil HUVFC biology, we found that Wnt3a treatment leads to phosphorylation of DVL3 and stabilization of beta-catenin. Moreover, under the same conditions we observed all upregulation in c-MYC, TIE-2 and GJA1 mRNA transcripts. Although treatment of HUVECs with Wnt5a induced DVL3 phosphorylation, we did not observe any of the other effects seen upon Wnt3a stimulation. Taken together, our data indicate that Wnt3a induces canonical and non-canonical Writ signaling in HUVECs, and stimulates their proliferation and migration. (C) 2009 Elsevier Inc. All rights reserved.