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Anti-migratory and anti-angiogenic effect of p16: A novel localization at membrane ruffles and lamellipodia in endothelial cells

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Abstract

Recent evidence has established different functions for the tumor suppressor protein, p16INK4A 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, αv-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 αvβ3-integrin-mediated migration.

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Authors and Affiliations

  1. Advancell, Barcelona, Catalonia, Spain

    Elena Alhaja, Roser Pagan & Senén Vilaró

  2. Merck Farma y Química, Laboratori de Bioinvestigació (LBI),Parc Científic de Barcelona, Josep Samitier1–5, Barcelona, Catalonia, 08028, Spain

    Jaume Adan, Francesc Mitjans & Jaume Piulats

  3. Departament Bioquímica i Biologia Molecular, Universitat de Barcelona, Barcelona, Catalonia, Spain

    Manel Cascalló & Adela Mazo

  4. Departament de Bioquímica i Biología Molecular, Facultat de Farmàcia, Div. IV, Universitat de Barcelona, Barcelona, Spain

    Mercè Rodríguez, Veronique Noé & Carlos J. Ciudad

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  1. Elena Alhaja
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Correspondence to Jaume Piulats.

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Alhaja, E., Adan, J., Pagan, R. et al. Anti-migratory and anti-angiogenic effect of p16: A novel localization at membrane ruffles and lamellipodia in endothelial cells. Angiogenesis 7, 323–333 (2004). https://doi.org/10.1007/s10456-005-0368-9

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