Anti-migratory and anti-angiogenic effect of p16: A novel localization at membrane ruffles and lamellipodia in endothelial cells
| Autor: | Mercè Rodríguez, Francesc Mitjans, Elena Alhaja, Jaume Piulats, Carlos J. Ciudad, Véronique Noé, Roser Pagan, Senén Vilaró, Adela Mazo, Jaume Adan, Manel Cascallo |
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| Rok vydání: | 2004 |
| Předmět: |
Cancer Research
Physiology Angiogenesis Clinical Biochemistry Neovascularization Physiologic Ezrin Cell Movement Humans Pseudopodia Enzyme Inhibitors Cells Cultured Cyclin-Dependent Kinase Inhibitor p16 Matrigel biology Cell Membrane Transfection Vinculin Integrin alphaVbeta3 Cyclin-Dependent Kinases rac GTP-Binding Proteins Cell biology Endothelial stem cell Focal Adhesion Protein-Tyrosine Kinases biology.protein Vitronectin Endothelium Vascular Lamellipodium Subcellular Fractions |
| Zdroj: | Angiogenesis. 7:323-333 |
| ISSN: | 1573-7209 0969-6970 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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