Tissue Factor Induced by Epithelial-Mesenchymal Transition Triggers a Procoagulant State That Drives Metastasis of Circulating Tumor Cells.
Identifieur interne : 001531 ( Main/Exploration ); précédent : 001530; suivant : 001532Tissue Factor Induced by Epithelial-Mesenchymal Transition Triggers a Procoagulant State That Drives Metastasis of Circulating Tumor Cells.
Auteurs : Morgane Bourcy [Belgique] ; Meggy Suarez-Carmona [Belgique] ; Justine Lambert [Belgique] ; Marie-Emilie Francart [Belgique] ; Hélène Schroeder [Belgique] ; Céline Delierneux [Belgique] ; Nicolas Skrypek [Belgique] ; Erik W. Thompson [Australie] ; Guy Jérusalem [Belgique] ; Geert Berx [Belgique] ; Marc Thiry [Belgique] ; Silvia Blacher [Belgique] ; Brett G. Hollier [Australie] ; Agnès Noël [Belgique] ; Cécile Oury [Belgique] ; Myriam Polette [France] ; Christine Gilles [Belgique]Source :
- Cancer research [ 1538-7445 ] ; 2016.
Descripteurs français
- KwdFr :
- Animaux, Cellules tumorales circulantes (anatomopathologie), Coagulation sanguine, Facteur de transcription Zeb1 (physiologie), Femelle, Humains, Lignée cellulaire tumorale, Souris, Souris de lignée BALB C, Thromboplastine (biosynthèse), Transition épithélio-mésenchymateuse, Tumeurs du poumon (secondaire).
- MESH :
- anatomopathologie : Cellules tumorales circulantes.
- biosynthèse : Thromboplastine.
- physiologie : Facteur de transcription Zeb1.
- secondaire : Tumeurs du poumon.
- Animaux, Coagulation sanguine, Femelle, Humains, Lignée cellulaire tumorale, Souris, Souris de lignée BALB C, Transition épithélio-mésenchymateuse.
English descriptors
- KwdEn :
- MESH :
- chemical , biosynthesis : Thromboplastin.
- pathology : Neoplastic Cells, Circulating.
- chemical , physiology : Zinc Finger E-box-Binding Homeobox 1.
- secondary : Lung Neoplasms.
- Animals, Blood Coagulation, Cell Line, Tumor, Epithelial-Mesenchymal Transition, Female, Humans, Mice, Mice, Inbred BALB C.
Abstract
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 CTCs with enhanced colonizing properties. Here we report that EMT induces tissue factor (TF), a major cell-associated initiator of coagulation and related procoagulant properties in the blood. TF blockade by antibody or shRNA diminished the procoagulant 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 that triggers local activation of coagulation pathways to support metastatic colonization of EMT-positive CTCs. Cancer Res; 76(14); 4270-82. ©2016 AACR.
DOI: 10.1158/0008-5472.CAN-15-2263
PubMed: 27221703
Affiliations:
- Australie, Belgique, France
- Champagne-Ardenne, Grand Est, Province de Flandre-Orientale, Province de Liège, Région flamande, Région wallonne
- Gand, Liège, Reims
- Université de Gand, Université de Liège
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Le document en format XML
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Department of Biomedical Molecular Biology, Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Unit of Molecular and Cellular Oncology Lab, Inflammation Research Center, VIB, Ghent, Belgium. Department of Biomedical Molecular Biology, Cancer Research Institute Ghent (CRIG), Ghent University, Ghent</wicri:regionArea><orgName type="university">Université de Gand</orgName><placeName><settlement type="city">Gand</settlement><region>Région flamande</region><region type="district" nuts="2">Province de Flandre-Orientale</region></placeName></affiliation></author><author><name sortKey="Thompson, Erik W" sort="Thompson, Erik W" uniqKey="Thompson E" first="Erik W" last="Thompson">Erik W. Thompson</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Health and Biomedical Innovation and School of Biomedical Sciences Translational Research Institute, Queensland University of Technology, Brisbane, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Institute of Health and Biomedical Innovation and School of Biomedical Sciences Translational Research Institute, Queensland University of Technology, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Jerusalem, Guy" sort="Jerusalem, Guy" uniqKey="Jerusalem G" first="Guy" last="Jérusalem">Guy Jérusalem</name><affiliation wicri:level="4"><nlm:affiliation>CHU, Department of Medical Oncology, University of Liège, Liège, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>CHU, Department of Medical Oncology, University of Liège, Liège</wicri:regionArea><orgName type="university">Université de Liège</orgName><placeName><settlement type="city">Liège</settlement><region type="region" nuts="1">Région wallonne</region><region type="province" nuts="1">Province de Liège</region></placeName></affiliation></author><author><name sortKey="Berx, Geert" sort="Berx, Geert" uniqKey="Berx G" first="Geert" last="Berx">Geert Berx</name><affiliation wicri:level="4"><nlm:affiliation>Unit of Molecular and Cellular Oncology Lab, Inflammation Research Center, VIB, Ghent, Belgium. Department of Biomedical Molecular Biology, Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Unit of Molecular and Cellular Oncology Lab, Inflammation Research Center, VIB, Ghent, Belgium. Department of Biomedical Molecular Biology, Cancer Research Institute Ghent (CRIG), Ghent University, Ghent</wicri:regionArea><orgName type="university">Université de Gand</orgName><placeName><settlement type="city">Gand</settlement><region>Région flamande</region><region type="district" nuts="2">Province de Flandre-Orientale</region></placeName></affiliation></author><author><name sortKey="Thiry, Marc" sort="Thiry, Marc" uniqKey="Thiry M" first="Marc" last="Thiry">Marc Thiry</name><affiliation wicri:level="4"><nlm:affiliation>GIGA-Neurosciences, Unit of Cell and Tissue Biology, University of Liège, Liège, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>GIGA-Neurosciences, Unit of Cell and Tissue Biology, University of Liège, Liège</wicri:regionArea><orgName type="university">Université de Liège</orgName><placeName><settlement type="city">Liège</settlement><region type="region" nuts="1">Région wallonne</region><region type="province" nuts="1">Province de Liège</region></placeName></affiliation></author><author><name sortKey="Blacher, Silvia" sort="Blacher, Silvia" uniqKey="Blacher S" first="Silvia" last="Blacher">Silvia Blacher</name><affiliation wicri:level="4"><nlm:affiliation>GIGA-Cancer, Laboratory of Tumor and Development Biology, University of Liège, Liège, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>GIGA-Cancer, Laboratory of Tumor and Development Biology, University of Liège, Liège</wicri:regionArea><orgName type="university">Université de Liège</orgName><placeName><settlement type="city">Liège</settlement><region type="region" nuts="1">Région wallonne</region><region type="province" nuts="1">Province de Liège</region></placeName></affiliation></author><author><name sortKey="Hollier, Brett G" sort="Hollier, Brett G" uniqKey="Hollier B" first="Brett G" last="Hollier">Brett G. Hollier</name><affiliation wicri:level="1"><nlm:affiliation>Australian Prostate Cancer Research Centre - Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, Brisbane, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Australian Prostate Cancer Research Centre - Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Noel, Agnes" sort="Noel, Agnes" uniqKey="Noel A" first="Agnès" last="Noël">Agnès Noël</name><affiliation wicri:level="4"><nlm:affiliation>GIGA-Cancer, Laboratory of Tumor and Development Biology, University of Liège, Liège, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>GIGA-Cancer, Laboratory of Tumor and Development Biology, University of Liège, Liège</wicri:regionArea><orgName type="university">Université de Liège</orgName><placeName><settlement type="city">Liège</settlement><region type="region" nuts="1">Région wallonne</region><region type="province" nuts="1">Province de Liège</region></placeName></affiliation></author><author><name sortKey="Oury, Cecile" sort="Oury, Cecile" uniqKey="Oury C" first="Cécile" last="Oury">Cécile Oury</name><affiliation wicri:level="4"><nlm:affiliation>GIGA-Cardiovascular Sciences, Laboratory of Thrombosis and Hemostasis, University of Liège, Liège, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>GIGA-Cardiovascular Sciences, Laboratory of Thrombosis and Hemostasis, University of Liège, Liège</wicri:regionArea><orgName type="university">Université de Liège</orgName><placeName><settlement type="city">Liège</settlement><region type="region" nuts="1">Région wallonne</region><region type="province" nuts="1">Province de Liège</region></placeName></affiliation></author><author><name sortKey="Polette, Myriam" sort="Polette, Myriam" uniqKey="Polette M" first="Myriam" last="Polette">Myriam Polette</name><affiliation wicri:level="3"><nlm:affiliation>INSERM UMR-S 903, CHU, Biopathology Laboratory, University of Reims, Reims, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM UMR-S 903, CHU, Biopathology Laboratory, University of Reims, Reims</wicri:regionArea><placeName><region type="region">Grand Est</region><region type="old region">Champagne-Ardenne</region><settlement type="city">Reims</settlement></placeName></affiliation></author><author><name sortKey="Gilles, Christine" sort="Gilles, Christine" uniqKey="Gilles C" first="Christine" last="Gilles">Christine Gilles</name><affiliation wicri:level="4"><nlm:affiliation>GIGA-Cancer, Laboratory of Tumor and Development Biology, University of Liège, Liège, Belgium. cgilles@ulg.ac.be.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>GIGA-Cancer, Laboratory of Tumor and Development Biology, University of Liège, Liège</wicri:regionArea><orgName type="university">Université de Liège</orgName><placeName><settlement type="city">Liège</settlement><region type="region" nuts="1">Région wallonne</region><region type="province" nuts="1">Province de Liège</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:27221703</idno><idno type="pmid">27221703</idno><idno type="doi">10.1158/0008-5472.CAN-15-2263</idno><idno type="wicri:Area/PubMed/Corpus">001B89</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001B89</idno><idno type="wicri:Area/PubMed/Curation">001B65</idno><idno type="wicri:explorRef" wicri:stream="PubMed" 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Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>GIGA-Cancer, Laboratory of Tumor and Development Biology, University of Liège, Liège</wicri:regionArea><orgName type="university">Université de Liège</orgName><placeName><settlement type="city">Liège</settlement><region type="region" nuts="1">Région wallonne</region><region type="province" nuts="1">Province de Liège</region></placeName></affiliation></author><author><name sortKey="Suarez Carmona, Meggy" sort="Suarez Carmona, Meggy" uniqKey="Suarez Carmona M" first="Meggy" last="Suarez-Carmona">Meggy Suarez-Carmona</name><affiliation wicri:level="4"><nlm:affiliation>GIGA-Cancer, Laboratory of Tumor and Development Biology, University of Liège, Liège, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>GIGA-Cancer, Laboratory of Tumor and Development Biology, University of Liège, Liège</wicri:regionArea><orgName type="university">Université de Liège</orgName><placeName><settlement type="city">Liège</settlement><region type="region" nuts="1">Région wallonne</region><region type="province" nuts="1">Province de Liège</region></placeName></affiliation></author><author><name sortKey="Lambert, Justine" sort="Lambert, Justine" uniqKey="Lambert J" first="Justine" last="Lambert">Justine Lambert</name><affiliation wicri:level="4"><nlm:affiliation>GIGA-Cancer, Laboratory of Tumor and Development Biology, University of Liège, Liège, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>GIGA-Cancer, Laboratory of Tumor and Development Biology, University of Liège, Liège</wicri:regionArea><orgName type="university">Université de Liège</orgName><placeName><settlement type="city">Liège</settlement><region type="region" nuts="1">Région wallonne</region><region type="province" nuts="1">Province de Liège</region></placeName></affiliation></author><author><name sortKey="Francart, Marie Emilie" sort="Francart, Marie Emilie" uniqKey="Francart M" first="Marie-Emilie" last="Francart">Marie-Emilie Francart</name><affiliation wicri:level="4"><nlm:affiliation>GIGA-Cancer, Laboratory of Tumor and Development Biology, University of Liège, Liège, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>GIGA-Cancer, Laboratory of Tumor and Development Biology, University of Liège, Liège</wicri:regionArea><orgName type="university">Université de Liège</orgName><placeName><settlement type="city">Liège</settlement><region type="region" nuts="1">Région wallonne</region><region type="province" nuts="1">Province de Liège</region></placeName></affiliation></author><author><name sortKey="Schroeder, Helene" sort="Schroeder, Helene" uniqKey="Schroeder H" first="Hélène" last="Schroeder">Hélène Schroeder</name><affiliation wicri:level="4"><nlm:affiliation>CHU, Department of Medical Oncology, University of Liège, Liège, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>CHU, Department of Medical Oncology, University of Liège, Liège</wicri:regionArea><orgName type="university">Université de Liège</orgName><placeName><settlement type="city">Liège</settlement><region type="region" nuts="1">Région wallonne</region><region type="province" nuts="1">Province de Liège</region></placeName></affiliation></author><author><name sortKey="Delierneux, Celine" sort="Delierneux, Celine" uniqKey="Delierneux C" first="Céline" last="Delierneux">Céline Delierneux</name><affiliation wicri:level="4"><nlm:affiliation>GIGA-Cardiovascular Sciences, Laboratory of Thrombosis and Hemostasis, University of Liège, Liège, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>GIGA-Cardiovascular Sciences, Laboratory of Thrombosis and Hemostasis, University of Liège, Liège</wicri:regionArea><orgName type="university">Université de Liège</orgName><placeName><settlement type="city">Liège</settlement><region type="region" nuts="1">Région wallonne</region><region type="province" nuts="1">Province de Liège</region></placeName></affiliation></author><author><name sortKey="Skrypek, Nicolas" sort="Skrypek, Nicolas" uniqKey="Skrypek N" first="Nicolas" last="Skrypek">Nicolas Skrypek</name><affiliation wicri:level="4"><nlm:affiliation>Unit of Molecular and Cellular Oncology Lab, Inflammation Research Center, VIB, Ghent, Belgium. Department of Biomedical Molecular Biology, Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Unit of Molecular and Cellular Oncology Lab, Inflammation Research Center, VIB, Ghent, Belgium. Department of Biomedical Molecular Biology, Cancer Research Institute Ghent (CRIG), Ghent University, Ghent</wicri:regionArea><orgName type="university">Université de Gand</orgName><placeName><settlement type="city">Gand</settlement><region>Région flamande</region><region type="district" nuts="2">Province de Flandre-Orientale</region></placeName></affiliation></author><author><name sortKey="Thompson, Erik W" sort="Thompson, Erik W" uniqKey="Thompson E" first="Erik W" last="Thompson">Erik W. Thompson</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Health and Biomedical Innovation and School of Biomedical Sciences Translational Research Institute, Queensland University of Technology, Brisbane, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Institute of Health and Biomedical Innovation and School of Biomedical Sciences Translational Research Institute, Queensland University of Technology, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Jerusalem, Guy" sort="Jerusalem, Guy" uniqKey="Jerusalem G" first="Guy" last="Jérusalem">Guy Jérusalem</name><affiliation wicri:level="4"><nlm:affiliation>CHU, Department of Medical Oncology, University of Liège, Liège, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>CHU, Department of Medical Oncology, University of Liège, Liège</wicri:regionArea><orgName type="university">Université de Liège</orgName><placeName><settlement type="city">Liège</settlement><region type="region" nuts="1">Région wallonne</region><region type="province" nuts="1">Province de Liège</region></placeName></affiliation></author><author><name sortKey="Berx, Geert" sort="Berx, Geert" uniqKey="Berx G" first="Geert" last="Berx">Geert Berx</name><affiliation wicri:level="4"><nlm:affiliation>Unit of Molecular and Cellular Oncology Lab, Inflammation Research Center, VIB, Ghent, Belgium. Department of Biomedical Molecular Biology, Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>Unit of Molecular and Cellular Oncology Lab, Inflammation Research Center, VIB, Ghent, Belgium. Department of Biomedical Molecular Biology, Cancer Research Institute Ghent (CRIG), Ghent University, Ghent</wicri:regionArea><orgName type="university">Université de Gand</orgName><placeName><settlement type="city">Gand</settlement><region>Région flamande</region><region type="district" nuts="2">Province de Flandre-Orientale</region></placeName></affiliation></author><author><name sortKey="Thiry, Marc" sort="Thiry, Marc" uniqKey="Thiry M" first="Marc" last="Thiry">Marc Thiry</name><affiliation wicri:level="4"><nlm:affiliation>GIGA-Neurosciences, Unit of Cell and Tissue Biology, University of Liège, Liège, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>GIGA-Neurosciences, Unit of Cell and Tissue Biology, University of Liège, Liège</wicri:regionArea><orgName type="university">Université de Liège</orgName><placeName><settlement type="city">Liège</settlement><region type="region" nuts="1">Région wallonne</region><region type="province" nuts="1">Province de Liège</region></placeName></affiliation></author><author><name sortKey="Blacher, Silvia" sort="Blacher, Silvia" uniqKey="Blacher S" first="Silvia" last="Blacher">Silvia Blacher</name><affiliation wicri:level="4"><nlm:affiliation>GIGA-Cancer, Laboratory of Tumor and Development Biology, University of Liège, Liège, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>GIGA-Cancer, Laboratory of Tumor and Development Biology, University of Liège, Liège</wicri:regionArea><orgName type="university">Université de Liège</orgName><placeName><settlement type="city">Liège</settlement><region type="region" nuts="1">Région wallonne</region><region type="province" nuts="1">Province de Liège</region></placeName></affiliation></author><author><name sortKey="Hollier, Brett G" sort="Hollier, Brett G" uniqKey="Hollier B" first="Brett G" last="Hollier">Brett G. Hollier</name><affiliation wicri:level="1"><nlm:affiliation>Australian Prostate Cancer Research Centre - Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, Brisbane, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Australian Prostate Cancer Research Centre - Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Noel, Agnes" sort="Noel, Agnes" uniqKey="Noel A" first="Agnès" last="Noël">Agnès Noël</name><affiliation wicri:level="4"><nlm:affiliation>GIGA-Cancer, Laboratory of Tumor and Development Biology, University of Liège, Liège, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>GIGA-Cancer, Laboratory of Tumor and Development Biology, University of Liège, Liège</wicri:regionArea><orgName type="university">Université de Liège</orgName><placeName><settlement type="city">Liège</settlement><region type="region" nuts="1">Région wallonne</region><region type="province" nuts="1">Province de Liège</region></placeName></affiliation></author><author><name sortKey="Oury, Cecile" sort="Oury, Cecile" uniqKey="Oury C" first="Cécile" last="Oury">Cécile Oury</name><affiliation wicri:level="4"><nlm:affiliation>GIGA-Cardiovascular Sciences, Laboratory of Thrombosis and Hemostasis, University of Liège, Liège, Belgium.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>GIGA-Cardiovascular Sciences, Laboratory of Thrombosis and Hemostasis, University of Liège, Liège</wicri:regionArea><orgName type="university">Université de Liège</orgName><placeName><settlement type="city">Liège</settlement><region type="region" nuts="1">Région wallonne</region><region type="province" nuts="1">Province de Liège</region></placeName></affiliation></author><author><name sortKey="Polette, Myriam" sort="Polette, Myriam" uniqKey="Polette M" first="Myriam" last="Polette">Myriam Polette</name><affiliation wicri:level="3"><nlm:affiliation>INSERM UMR-S 903, CHU, Biopathology Laboratory, University of Reims, Reims, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM UMR-S 903, CHU, Biopathology Laboratory, University of Reims, Reims</wicri:regionArea><placeName><region type="region">Grand Est</region><region type="old region">Champagne-Ardenne</region><settlement type="city">Reims</settlement></placeName></affiliation></author><author><name sortKey="Gilles, Christine" sort="Gilles, Christine" uniqKey="Gilles C" first="Christine" last="Gilles">Christine Gilles</name><affiliation wicri:level="4"><nlm:affiliation>GIGA-Cancer, Laboratory of Tumor and Development Biology, University of Liège, Liège, Belgium. cgilles@ulg.ac.be.</nlm:affiliation><country xml:lang="fr">Belgique</country><wicri:regionArea>GIGA-Cancer, Laboratory of Tumor and Development Biology, University of Liège, Liège</wicri:regionArea><orgName type="university">Université de Liège</orgName><placeName><settlement type="city">Liège</settlement><region type="region" nuts="1">Région wallonne</region><region type="province" nuts="1">Province de Liège</region></placeName></affiliation></author></analytic><series><title level="j">Cancer research</title><idno type="eISSN">1538-7445</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Blood Coagulation</term><term>Cell Line, Tumor</term><term>Epithelial-Mesenchymal Transition</term><term>Female</term><term>Humans</term><term>Lung Neoplasms (secondary)</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Neoplastic Cells, Circulating (pathology)</term><term>Thromboplastin (biosynthesis)</term><term>Zinc Finger E-box-Binding Homeobox 1 (physiology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Cellules tumorales circulantes (anatomopathologie)</term><term>Coagulation sanguine</term><term>Facteur de transcription Zeb1 (physiologie)</term><term>Femelle</term><term>Humains</term><term>Lignée cellulaire tumorale</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Thromboplastine (biosynthèse)</term><term>Transition épithélio-mésenchymateuse</term><term>Tumeurs du poumon (secondaire)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Thromboplastin</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Cellules tumorales circulantes</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Thromboplastine</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Neoplastic Cells, Circulating</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Facteur de transcription Zeb1</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Zinc Finger E-box-Binding Homeobox 1</term></keywords><keywords scheme="MESH" qualifier="secondaire" xml:lang="fr"><term>Tumeurs du poumon</term></keywords><keywords scheme="MESH" qualifier="secondary" xml:lang="en"><term>Lung Neoplasms</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Blood Coagulation</term><term>Cell Line, Tumor</term><term>Epithelial-Mesenchymal Transition</term><term>Female</term><term>Humans</term><term>Mice</term><term>Mice, Inbred BALB C</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Coagulation sanguine</term><term>Femelle</term><term>Humains</term><term>Lignée cellulaire tumorale</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Transition épithélio-mésenchymateuse</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="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 CTCs with enhanced colonizing properties. Here we report that EMT induces tissue factor (TF), a major cell-associated initiator of coagulation and related procoagulant properties in the blood. TF blockade by antibody or shRNA diminished the procoagulant 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 that triggers local activation of coagulation pathways to support metastatic colonization of EMT-positive CTCs. Cancer Res; 76(14); 4270-82. ©2016 AACR.</div></front></TEI><affiliations><list><country><li>Australie</li><li>Belgique</li><li>France</li></country><region><li>Champagne-Ardenne</li><li>Grand Est</li><li>Province de Flandre-Orientale</li><li>Province de Liège</li><li>Région flamande</li><li>Région wallonne</li></region><settlement><li>Gand</li><li>Liège</li><li>Reims</li></settlement><orgName><li>Université de Gand</li><li>Université de Liège</li></orgName></list><tree><country name="Belgique"><region name="Région wallonne"><name sortKey="Bourcy, Morgane" sort="Bourcy, Morgane" uniqKey="Bourcy M" first="Morgane" last="Bourcy">Morgane Bourcy</name></region><name sortKey="Berx, Geert" sort="Berx, Geert" uniqKey="Berx G" first="Geert" last="Berx">Geert Berx</name><name sortKey="Blacher, Silvia" sort="Blacher, Silvia" uniqKey="Blacher S" first="Silvia" last="Blacher">Silvia Blacher</name><name sortKey="Delierneux, Celine" sort="Delierneux, Celine" uniqKey="Delierneux C" first="Céline" last="Delierneux">Céline Delierneux</name><name sortKey="Francart, Marie Emilie" sort="Francart, Marie Emilie" uniqKey="Francart M" first="Marie-Emilie" last="Francart">Marie-Emilie Francart</name><name sortKey="Gilles, Christine" sort="Gilles, Christine" uniqKey="Gilles C" first="Christine" last="Gilles">Christine Gilles</name><name sortKey="Jerusalem, Guy" sort="Jerusalem, Guy" uniqKey="Jerusalem G" first="Guy" last="Jérusalem">Guy Jérusalem</name><name sortKey="Lambert, Justine" sort="Lambert, Justine" uniqKey="Lambert J" first="Justine" last="Lambert">Justine Lambert</name><name sortKey="Noel, Agnes" sort="Noel, Agnes" uniqKey="Noel A" first="Agnès" last="Noël">Agnès Noël</name><name sortKey="Oury, Cecile" sort="Oury, Cecile" uniqKey="Oury C" first="Cécile" last="Oury">Cécile Oury</name><name sortKey="Schroeder, Helene" sort="Schroeder, Helene" uniqKey="Schroeder H" first="Hélène" last="Schroeder">Hélène Schroeder</name><name sortKey="Skrypek, Nicolas" sort="Skrypek, Nicolas" uniqKey="Skrypek N" first="Nicolas" last="Skrypek">Nicolas Skrypek</name><name sortKey="Suarez Carmona, Meggy" sort="Suarez Carmona, Meggy" uniqKey="Suarez Carmona M" first="Meggy" last="Suarez-Carmona">Meggy Suarez-Carmona</name><name sortKey="Thiry, Marc" sort="Thiry, Marc" uniqKey="Thiry M" first="Marc" last="Thiry">Marc Thiry</name></country><country name="Australie"><noRegion><name sortKey="Thompson, Erik W" sort="Thompson, Erik W" uniqKey="Thompson E" first="Erik W" last="Thompson">Erik W. Thompson</name></noRegion><name sortKey="Hollier, Brett G" sort="Hollier, Brett G" uniqKey="Hollier B" first="Brett G" last="Hollier">Brett G. Hollier</name></country><country name="France"><region name="Grand Est"><name sortKey="Polette, Myriam" sort="Polette, Myriam" uniqKey="Polette M" first="Myriam" last="Polette">Myriam Polette</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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