Advertisement
Advertisement

Contact Person

Dr. Elinor Switzer

Managing Editor

Phone: +49 (0)711 - 2 29 87 63
Fax: +49 (0)711 - 2 29 87 65
send an Email


Archive

Formation of tissue factor-factor VIIa-factor Xa complex induces activation of the mTOR pathway which regulates migration of human breast cancer cells

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
DOI: http://dx.doi.org/10.1160/TH07-12-0722
Issue: 2008: 100/1 (July) pp. 1-171
Pages: 127-133

Formation of tissue factor-factor VIIa-factor Xa complex induces activation of the mTOR pathway which regulates migration of human breast cancer cells

Xiaofeng Jiang1, Shimei Zhu2, Tracee S. Panetti1, Michael E. Bromberg1
1Sol Sherry Thrombosis Research Center, 2Department of Anatomy, Temple University School of Medicine, Philadelphia, Pennsylvania, USA

Keywords

breast cancer, Tissue factor, factor Xa, factorVIIa, mammalian target of rapamycin

Summary

Tissue factor (TF) is a transmembrane glycoprotein that initiates blood coagulation when complexed with activated factor VII (FVIIa).TF is constitutively expressed in a variety of tumor cells and has been implicated in cellular signaling, angiogenesis, and tumor progression. Formation of TF-FVIIa complex and generation of downstream coagulation proteases, including activated factor X (FXa) and thrombin, initiate signaling by activation of protease-activated receptors (PARs).We have previously shown thatTF-FVIIa-Xa complex formation promotes phosphorylation of p44/42 mitogen-activated protein kinase and Akt/protein kinase B in human breast cancer cells. In the present study, we show that formation of TF-FVIIa-FXa complex induces phosphorylation of mammalian target of rapamycin (mTOR) and p70 S6 kinase in a human breast cancer cell line, Adr-MCF-7. Activation of the mTOR pathway, which is probably mediated by PAR1 and/or PAR2, was associated with enhanced cell migration, a key step in the metastatic cascade. Inhibition of this pathway with the specific mTOR inhibitor, rapamycin, markedly decreased cell migration induced by formation of TF-FVIIa-FXa complex.These studies suggest that TF-FVIIa-mediated signaling modulates mTOR pathway activation, which regulates in part breast cancer cell migration.Targeting the TF-mediated cell signaling pathway might represent a novel strategy for the treatment of breast cancer.

You may also be interested in...

1.
Xiaofeng Jiang 1 , Yan Lin Guo2 , Michael E. Bromberg1

Thromb Haemost 2006 96 2: 196-201

http://dx.doi.org/10.1160/TH06-01-0057

2.
Rômulo A. Nazareth 1 , Luana S. Tomaz 1 , Susana Ortiz-Costa2 , Geórgia C. Atella 1 , José M. C. Ribeiro 3 , Ivo M. B. Francischetti3 , Robson Q. Monteiro 1

Thromb Haemost 2006 96 1: 7-13

http://dx.doi.org/10.1160/TH06-02-0105

3.
Helene F. S. Negaard1,4, Per Ole Iversen1,4, Bjørn Østenstad2, Nina Iversen3, Pål A. Holme5, Per Morten Sandset1,4

Thromb Haemost 2008 99 6: 1040-1048

http://dx.doi.org/10.1160/TH07-09-0541