title: Wnt3a regulates proliferation and migration of HUVEC via canonical and non-canonical Wnt signaling pathways.
abstract: 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 on HUVEC biology, we found that Wnt3a treatment leads to phosphorylation of DVL3 and stabilization of beta-catenin. Moreover, under the same conditions we observed an 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 Wnt signaling in HUVECs, and stimulates their proliferation and migration.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors.forename: Ivana
authors.initials: I
authors.lastname: Samarzija
authors.forename: Patrizia
authors.initials: P
authors.lastname: Sini
authors.forename: Thomas
authors.initials: T
authors.lastname: Schlange
authors.forename: Gwen
authors.initials: G
authors.lastname: Macdonald
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Hynes
mesh_terms: D002465:Cell Movement; D049109:Cell Proliferation; D018031:Connexin 43 / Q000235:genetics; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051157:Frizzled Receptors / Q000235:genetics; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics; D042787:Receptor, TIE-2 / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D015398:Signal Transduction; D014158:Transcription, Genetic; D014470:Umbilical Cord / Q000166:cytology; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D000071818:Wnt-5a Protein; D060508:Wnt3 Protein; D060509:Wnt3A Protein
chemical_list: D018031:Connexin 43; C402930:FZD4 protein, human; C484687:FZD6 protein, human; D051157:Frizzled Receptors; C500216:GJA1 protein, human; C489427:MYC protein, human; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D043562:Receptors, G-Protein-Coupled; C555510:WNT3A protein, human; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D042787:Receptor, TIE-2