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

[1] Regulation of vascular endothelial growth factor production and angiogenesis by the cytoplasmic tail of tissue factor [J].

Abe, K ;

Shoji, M ;

Chen, J ;

Bierhaus, A ;

Danave, I ;

Micko, C ;

Casper, K ;

Dillehay, DL ;

Nawroth, PP ;

Rickles, FR .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (15) :8663-8668

[2] PHAGOKINETIC TRACKS OF 3T3-CELLS [J].

ALBRECHTBUEHLER, G .

CELL, 1977, 11 (02) :395-404

[3]

Amirkhosravi A, 2002, THROMB HAEMOSTASIS, V87, P930

[4] Semaphorin 3A-vascular endothelial growth factor-165 balance mediates migration and apoptosis of neural progenitor cells by the recruitment of shared receptor [J].

Bagnard, D ;

Vaillant, C ;

Khuth, ST ;

Dufay, N ;

Lohrum, M ;

Püschel, AW ;

Belin, MF ;

Bolz, J ;

Thomasset, N .

JOURNAL OF NEUROSCIENCE, 2001, 21 (10) :3332-3341

[5] Signaling of the tissue factor coagulation pathway in angiogenesis and cancer [J].

Belting, M ;

Ahamed, J ;

Ruf, W .

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2005, 25 (08) :1545-1550

[6] The magic of the hypoxia-signaling cascade [J].

Benizri, E. ;

Ginouves, A. ;

Berra, E. .

CELLULAR AND MOLECULAR LIFE SCIENCES, 2008, 65 (7-8) :1133-1149

[7]

Bohm SK, 1996, J BIOL CHEM, V271, P22003

[8] TISSUE FACTOR PROMOTES MELANOMA METASTASIS BY A PATHWAY INDEPENDENT OF BLOOD-COAGULATION [J].

BROMBERG, ME ;

KONIGSBERG, WH ;

MADISON, JF ;

PAWASHE, A ;

GAREN, A .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (18) :8205-8209

[9] Tissue factor- and factor X-dependent activation of protease-activated receptor 2 by factor VIIa [J].

Camerer, E ;

Huang, W ;

Coughlin, SR .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (10) :5255-5260

[10]

Chen J, 2001, THROMB HAEMOSTASIS, V86, P334

← 1 2 3 4 5 6 →