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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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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DOI: https://doi.org/10.1007/s10456-005-0368-9