↓ Skip to main content

Cross-talk between the Tissue Factor/coagulation factor VIIa complex and the tyrosine kinase receptor EphA2 in cancer

Overview of attention for article published in BMC Cancer, May 2016
Altmetric Badge

Citations

dimensions_citation
9 Dimensions

Readers on

mendeley
28 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
Cross-talk between the Tissue Factor/coagulation factor VIIa complex and the tyrosine kinase receptor EphA2 in cancer
Published in
BMC Cancer, May 2016
DOI 10.1186/s12885-016-2375-1
Pubmed ID
Authors

Oskar Eriksson, Åsa Thulin, Anna Asplund, Geeta Hegde, Sanjay Navani, Agneta Siegbahn

Abstract

Tissue Factor (TF) forms a proteolytically active complex together with coagulation factor VIIa (FVIIa) and functions as the trigger of blood coagulation or alternatively activates cell signaling. We recently described that EphA2 of the Eph tyrosine kinase receptor family is cleaved directly by the TF/FVIIa complex. The aim of the present study was to further characterize the cross-talk between TF/FVIIa and EphA2 using in vitro model systems and human cancer specimens. Cleavage and phosphorylation of EphA2 was studied by Western blot. Subcellular localization of TF and EphA2 was investigated by a proximity ligation assay and confocal microscopy. Phalloidin staining of the actin cytoskeleton was used to study cell rounding and retraction fiber formation. Expression of TF and EphA2 in human colorectal cancer specimens was examined by immunohistochemistry. TF and EphA2 co-localized constitutively in MDA-MB-231 cells, and addition of FVIIa resulted in cleavage of EphA2 by a PAR2-independent mechanism. Overexpression of TF in U251 glioblastoma cells lead to co-localization with EphA2 at the leading edge and FVIIa-dependent cleavage of EphA2. FVIIa potentiated ephrin-A1-induced cell rounding and retraction fiber formation in MDA-MB-231 cells through a RhoA/ROCK-dependent pathway that did not require PAR2-activation. TF and EphA2 were expressed in colorectal cancer specimens, and were significantly correlated. These results suggest that TF/FVIIa-EphA2 cross-talk might potentiate ligand-dependent EphA2 signaling in human cancers, and provide initial evidence that it is possible for this interaction to occur in vivo.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 28 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 4%
Unknown 27 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 21%
Student > Master 5 18%
Researcher 3 11%
Professor > Associate Professor 2 7%
Student > Bachelor 1 4%
Other 1 4%
Unknown 10 36%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 4 14%
Medicine and Dentistry 4 14%
Agricultural and Biological Sciences 3 11%
Immunology and Microbiology 2 7%
Neuroscience 1 4%
Other 3 11%
Unknown 11 39%