Cortactin activation by FVIIa/tissue factor and PAR2 promotes endothelial cell migration

被引：12

作者：

Zhu, Tang ^{[1
]}

Mancini, Joseph A. ^{[1
]}

Sapieha, Przemyslaw ^{[3
]}

Yang, Chun ^{[1
]}

Joyal, Jean-Sebastien ^{[1
]}

Honore, Jean-Claude ^{[1
]}

Leduc, Martin ^{[1
]}

Zaniolo, Karine ^{[1
]}

Hardy, Pierre ^{[1
]}

Shao, Zhuo ^{[1
]}

Fan, Li ^{[2
]}

Hou, Xin ^{[1
]}

Rivard, Georges-Etienne ^{[2
]}

Chemtob, Sylvain ^{[1
]}

机构：

[1] CHU Ste Justine, Res Ctr, Dept Pediat, Montreal, PQ H3T 1C5, Canada

[2] CHU Ste Justine, Res Ctr, Dept Hematol, Montreal, PQ H3T 1C5, Canada

[3] Univ Montreal, Dept Ophthalmol, Maisonneuve Rosemont Hosp Res Ctr, Montreal, PQ, Canada

来源：

AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY | 2011年 / 300卷 / 03期

关键词：

angiogenesis; lamellipodia; RhoA; FACTOR CYTOPLASMIC DOMAIN; TISSUE-FACTOR; FACTOR-VIIA; CANCER-CELLS; EXTRACELLULAR-MATRIX; RECEPTOR; CHEMOTAXIS; PATHWAY; GROWTH; ASSAY;

D O I：

10.1152/ajpregu.00137.2010

中图分类号：

Q4 [生理学];

学科分类号：

071003 ;

摘要：

Cellular migration is a complex process that requires the polymerization of actin filaments to drive cellular extension. Smooth muscle and cancer cell migration has been shown to be affected by coagulation factors, notably the factor VII (FVIIa) and tissue factor (TF) complex. The present studies delineated mediators involved with the process of FVIIa/TF-induced cell migration and utilized a simple, precise, and reproducible, migration assay. Both FVIIa and protease-activated receptor-2 (PAR2)-activating peptide, SLIGRL, increased the migration rate of porcine cerebral microvascular endothelial cells (pCMVECs) overexpressing human TF. Ras homolog gene family member A (RhoA) and cortactin were upregulated during the process; expression of HIF, actin polymerization nuclear diaphanous-related formin-1 and -2 (Dia1, and Dia2) were unaffected. Gene silencing by shRNA to PAR2, RhoA, and cortactin attenuated this gene upregulation and migration induced by FVIIa/TF. Utilizing immunocellular localization, we demonstrate that during FVIIa/TF and PAR2 activation, cortactin molecules translocate from the cytoplasm to the cell periphery and assist in lamellipodia formation of pCMVECs. Overall, we demonstrate a novel regulation and role for cortactin in FVIIa/TF-mediated endothelial cell migration that occurs through a PAR2 and RhoA dependent mechanism.

引用

页码：R577 / R585

页数：9

共 53 条

[31] Targeted deletion of the cytosolic domain of tissue factor in mice does not affect development [J].

Melis, E ;

Moons, L ;

De Mol, M ;

Herbert, JM ;

Mackman, N ;

Collen, D ;

Carmeliet, P ;

Dewerchin, M .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2001, 286 (03) :580-586

[32] Tissue Factor and Cancer [J].

Milsom, Chloe ;

Rak, Janusz .

PATHOPHYSIOLOGY OF HAEMOSTASIS AND THROMBOSIS, 2007, 36 (3-4) :160-176

[33] RAPID COLORIMETRIC ASSAY FOR CELLULAR GROWTH AND SURVIVAL - APPLICATION TO PROLIFERATION AND CYTO-TOXICITY ASSAYS [J].

MOSMANN, T .

JOURNAL OF IMMUNOLOGICAL METHODS, 1983, 65 (1-2) :55-63

[34] Tissue factor cytoplasmic domain stimulates migration by activation of the GTPase Rac1 and the mitogen-activated protein kinase p38 [J].

Ott, I ;

Weigand, B ;

Michl, R ;

Seitz, I ;

Sabbari-Erfani, N ;

Neumann, FJ ;

Schömig, A .

CIRCULATION, 2005, 111 (03) :349-355

[35] The Rho family GTPase Rif induces filopodia through mDia2 [J].

Pellegrin, S ;

Mellor, H .

CURRENT BIOLOGY, 2005, 15 (02) :129-133

[36] Disruption of the diaphanous-related formin Drf1 gene encoding mDia1 reveals a role for Drf3 as an effector for Cdc42 [J].

Peng, J ;

Wallar, BJ ;

Flanders, A ;

Swiatek, PJ ;

Alberts, AS .

CURRENT BIOLOGY, 2003, 13 (07) :534-545

[37] Spatiotemporal dynamics of RhoA activity in migrating cells [J].

Pertz, O ;

Hodgson, L ;

Klemke, RL ;

Hahn, KM .

NATURE, 2006, 440 (7087) :1069-1072

[38] Microarray studies of factor VIIa-activated cancer cells [J].

Petersen, Lars Christian .

THROMBOSIS RESEARCH, 2008, 122 :S11-S13

[39]

PRATT BM, 1984, AM J PATHOL, V117, P349

[40] LEUKOCYTE MIGRATION AGAROSE TEST FOR ASSESSMENT OF HUMAN NEUTROPHIL CHEMOTAXIS .2. VARIABLES IN ATTRACTION ASSAY [J].

REPO, H ;

KOSUNEN, TU .

SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 1977, 6 (03) :211-218

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