title: Anti-migratory and anti-angiogenic effect of p16: a novel localization at membrane ruffles and lamellipodia in endothelial cells.
abstract: Recent evidence has established different functions for the tumor suppressor protein, p16(INK4A) aside from controlling the cell cycle. Here we report that cdk4/6 inhibition blocked both human umbilical vein endothelial cells (HUVEC) spreading on a vitronectin matrix and HUVEC migration on vitronectin. p16 can also act as an anti-angiogenic molecule in vitro since HUVEC and HMEC cells transfected with Ad-p16 or treated with Antennapedia p16 peptides are unable to differentiate on a Matrigel matrix. Both, p16, cyclin D1, cdk4 and cdk6 were immuno-colocalized with Ezrin, Rac, Vinculin, alphav-integrin, and FAK proteins in the ruffles and lamellipodia of migratory cells. Our results indicate that p16 is a key component of a new cytoplasmic pathway controlling angiogenesis of endothelial cells via the alphavbeta3-integrin-mediated migration.
authors.affiliation: Advancell, Barcelona, Catalonia, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Alhaja
authors.forename: Jaume
authors.initials: J
authors.lastname: Adan
authors.forename: Roser
authors.initials: R
authors.lastname: Pagan
authors.forename: Francesc
authors.initials: F
authors.lastname: Mitjans
authors.forename: Manel
authors.initials: M
authors.lastname: Cascalló
authors.forename: Mercè
authors.initials: M
authors.lastname: Rodríguez
authors.forename: Veronique
authors.initials: V
authors.lastname: Noé
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Ciudad
authors.forename: Adela
authors.initials: A
authors.lastname: Mazo
authors.forename: Senén
authors.initials: S
authors.lastname: Vilaró
authors.forename: Jaume
authors.initials: J
authors.lastname: Piulats
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism / Q000502:physiology*; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011554:Pseudopodia / Q000378:metabolism*; D013347:Subcellular Fractions / Q000201:enzymology / Q000378:metabolism; D016596:Vinculin / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004791:Enzyme Inhibitors; D039302:Integrin alphaVbeta3; D016596:Vinculin; D051416:Focal Adhesion Protein-Tyrosine Kinases; D018844:Cyclin-Dependent Kinases; D020744:rac GTP-Binding Proteins