Article (Scientific journals)
Tissue factor induced by epithelial-mesenchymal transition triggers a pro-coagulant state that drives metastasis of circulating tumor cells.
Bourcy, Morgane; Suarez-Carmona, Meggy; Lambert, Justine et al.
2016In Cancer Research, 76 (14), p. 4270-4282
Peer Reviewed verified by ORBi
 

Files


Full Text
2016-Bourcy- Version finale.pdf
Publisher postprint (1.81 MB)
Download

All documents in ORBi are protected by a user license.

Send to



Details



Keywords :
pithelial-mesenchymal transition; Coagulation; Circulating tumor cells
Abstract :
[en] Epithelial-mesenchymal transition (EMT) is prominent in circulating tumor cells (CTC), but how it influences metastatic spread in this setting is obscure. Insofar as blood provides a specific microenvironment for tumor cells, we explored a potential link between EMT and coagulation that may provide EMT-positive CTC with enhanced colonizing properties. Here we report that EMT induces tissue factor (TF), a major cell-associated initiator of coagulation and related pro-coagulant properties in the blood. TF blockade by antibody or shRNA diminished the pro-coagulant activity of EMT-positive cells, confirming a functional role for TF in these processes. Silencing the EMT transcription factor ZEB1 inhibited both EMT-associated TF expression and coagulant activity, further strengthening the link between EMT and coagulation. Accordingly, EMT-positive cells exhibited a higher persistance/survival in the lungs of mice colonized after intravenous injection, a feature diminished by TF or ZEB1 silencing. In tumor cells with limited metastatic capability, enforcing expression of the EMT transcription factor Snail increased TF, coagulant properties and early metastasis. Clinically, we identified a subpopulation of CTC expressing vimentin and TF in the blood of metastatic breast cancer patients consistent with our observations. Overall, our findings define a novel EMT-TF regulatory axis which triggers local activation of coagulation pathways to support metastatic colonization of EMT-positive CTC.
Disciplines :
Oncology
Author, co-author :
Bourcy, Morgane ;  Université de Liège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Suarez-Carmona, Meggy 
Lambert, Justine ;  Université de Liège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Francart, Marie-Emilie ;  Université de Liège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
SCHROEDER, Hélène ;  Centre Hospitalier Universitaire de Liège - CHU > Centre d'oncologie
Delierneux, Céline ;  Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R : GIGA - Cardiovascular Sciences
Skrypek, Nicolas
Thompson, Erik W.
JERUSALEM, Guy  ;  Centre Hospitalier Universitaire de Liège - CHU > Service d'oncologie médicale
Berx, Geert
Thiry, Marc  ;  Université de Liège > Département des sciences de la vie > GIGA-R : Biologie cellulaire
Blacher, Silvia ;  Université de Liège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Hollier, Breet G.
Noël, Agnès ;  Université de Liège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Oury, Cécile  ;  Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R : GIGA - Cardiovascular Sciences
Polette, Myriam
Gilles, Christine ;  Université de Liège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
More authors (7 more) Less
Language :
English
Title :
Tissue factor induced by epithelial-mesenchymal transition triggers a pro-coagulant state that drives metastasis of circulating tumor cells.
Publication date :
2016
Journal title :
Cancer Research
ISSN :
0008-5472
eISSN :
1538-7445
Publisher :
American Association for Cancer Research, Inc. (AACR), Baltimore, United States - Maryland
Volume :
76
Issue :
14
Pages :
4270-4282
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 27 May 2016

Statistics


Number of views
102 (33 by ULiège)
Number of downloads
154 (8 by ULiège)

Bibliography


Similar publications



Contact ORBi