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

被引：31

作者：

Alhaja E. ^{[1
]}

Adan J. ^{[2
]}

Pagan R. ^{[1
]}

Mitjans F. ^{[2
]}

Cascalló M. ^{[3
]}

Rodríguez M. ^{[4
]}

Noé V. ^{[4
]}

Ciudad C.J. ^{[4
]}

Mazo A. ^{[3
]}

Vilaró S. ^{[1
]}

Piulats J. ^{[2
,5
]}

机构：

[1] Advancell, Barcelona, Catalonia

[2] Merck Farma Y Química, Laboratori de Bioinvestigació (LBI), Barcelona, Catalonia

[3] Departament Bioquímica I Biologia Molecular, Universitat de Barcelona, Barcelona, Catalonia

[4] Departament de Bioquímica I Biología Molecular, Facultat de Farmàcia, Universitat de Barcelona, Barcelona

[5] Laboratori de Bioinvestigació, Merck Farma Y Química, Parc Científic de Barcelona, 08028 Barcelona, Catalonia

来源：

Angiogenesis | 2004年 / 7卷 / 4期

关键词：

Angiogenesis; CDK inhibitors; Lamellipodia; Migration; p16; Rac;

D O I：

10.1007/s10456-005-0368-9

中图分类号：

学科分类号：

摘要：

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. © Springer 2005.

引用

页码：323 / 333

页数：10

共 42 条

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