Formation of tissue factor-factor VIIa-factor Xa complex induces activation of the mTOR pathway which regulates migration of human breast cancer cells
| Autor: | Michael E. Bromberg, Tracee S. Panetti, Shimei Zhu, Xiaofeng Jiang |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Cell signaling
Morpholines Breast Neoplasms Factor VIIa Biology mTORC2 Thromboplastin Tissue factor Cell Movement Cell Line Tumor Humans Receptor PAR-2 Neoplasm Invasiveness Receptor PAR-1 Phosphorylation Protein kinase A Protein Kinase Inhibitors Protein kinase B PI3K/AKT/mTOR pathway Sirolimus Akt/PKB signaling pathway TOR Serine-Threonine Kinases RPTOR Ribosomal Protein S6 Kinases 70-kDa Hematology Recombinant Proteins Cell biology Biochemistry Chromones Factor Xa Female Peptides Protein Kinases Proto-Oncogene Proteins c-akt |
| Zdroj: | Thrombosis and Haemostasis. 100:127-133 |
| ISSN: | 2567-689X 0340-6245 |
| Popis: | SummaryTissue 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 thatTFFVIIa-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 TFFVIIa-FXa complex. These studies suggest thatTFFVIIa-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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|