PROX1 promotes metabolic adaptation and fuels outgrowth of Wnt(high) metastatic colon cancer cells.
Identifieur interne : 001011 ( Main/Exploration ); précédent : 001010; suivant : 001012PROX1 promotes metabolic adaptation and fuels outgrowth of Wnt(high) metastatic colon cancer cells.
Auteurs : Simone Ragusa [Suisse] ; Jianpin Cheng [Suisse] ; Konstantin I. Ivanov [Suisse] ; Nadine Zangger [Suisse] ; Fatih Ceteci [Royaume-Uni] ; Jeremiah Bernier-Latmani [Suisse] ; Stavros Milatos [Suisse] ; Jean-Marc Joseph [Suisse] ; Stephane Tercier [Suisse] ; Hanifa Bouzourene [Suisse] ; Fredrik T. Bosman [Suisse] ; Igor Letovanec [Suisse] ; Giancarlo Marra [Suisse] ; Michel Gonzalez [Suisse] ; Patrizia Cammareri [Royaume-Uni] ; Owen J. Sansom [Royaume-Uni] ; Mauro Delorenzi [Suisse] ; Tatiana V. Petrova [Suisse]Source :
- Cell reports [ 2211-1247 ] ; 2014.
Descripteurs français
- KwdFr :
- Animaux, Apoptose (), Cellules souches tumorales (métabolisme), Chloroquine (toxicité), Humains, Interférence par ARN, Lignée cellulaire tumorale, Métastase lymphatique, Noeuds lymphatiques (anatomopathologie), Prolifération cellulaire (), Protéines de type Wingless (métabolisme), Protéines proto-oncogènes c-bcl-2 (métabolisme), Protéines suppresseurs de tumeurs (antagonistes et inhibiteurs), Protéines suppresseurs de tumeurs (génétique), Protéines suppresseurs de tumeurs (métabolisme), Protéines à homéodomaine (antagonistes et inhibiteurs), Protéines à homéodomaine (génétique), Protéines à homéodomaine (métabolisme), Souris, Souris de lignée NOD, Stress physiologique, Techniques de culture cellulaire, Tumeurs du côlon (anatomopathologie), Tumeurs du côlon (mortalité), Tumeurs du côlon (métabolisme), Tumeurs du foie (anatomopathologie), Tumeurs du foie (secondaire), Tumeurs du poumon (anatomopathologie), Tumeurs du poumon (secondaire), Voie de signalisation Wnt.
- MESH :
- anatomopathologie : Noeuds lymphatiques, Tumeurs du côlon, Tumeurs du foie, Tumeurs du poumon.
- antagonistes et inhibiteurs : Protéines suppresseurs de tumeurs, Protéines à homéodomaine.
- génétique : Protéines suppresseurs de tumeurs, Protéines à homéodomaine.
- mortalité : Tumeurs du côlon.
- métabolisme : Cellules souches tumorales, Protéines de type Wingless, Protéines proto-oncogènes c-bcl-2, Protéines suppresseurs de tumeurs, Protéines à homéodomaine, Tumeurs du côlon.
- secondaire : Tumeurs du foie, Tumeurs du poumon.
- toxicité : Chloroquine.
- Animaux, Apoptose, Humains, Interférence par ARN, Lignée cellulaire tumorale, Métastase lymphatique, Prolifération cellulaire, Souris, Souris de lignée NOD, Stress physiologique, Techniques de culture cellulaire, Voie de signalisation Wnt.
English descriptors
- KwdEn :
- Animals, Apoptosis (drug effects), Cell Culture Techniques, Cell Line, Tumor, Cell Proliferation (drug effects), Chloroquine (toxicity), Colonic Neoplasms (metabolism), Colonic Neoplasms (mortality), Colonic Neoplasms (pathology), Homeodomain Proteins (antagonists & inhibitors), Homeodomain Proteins (genetics), Homeodomain Proteins (metabolism), Humans, Liver Neoplasms (pathology), Liver Neoplasms (secondary), Lung Neoplasms (pathology), Lung Neoplasms (secondary), Lymph Nodes (pathology), Lymphatic Metastasis, Mice, Mice, Inbred NOD, Neoplastic Stem Cells (metabolism), Proto-Oncogene Proteins c-bcl-2 (metabolism), RNA Interference, Stress, Physiological, Tumor Suppressor Proteins (antagonists & inhibitors), Tumor Suppressor Proteins (genetics), Tumor Suppressor Proteins (metabolism), Wnt Proteins (metabolism), Wnt Signaling Pathway.
- MESH :
- chemical , antagonists & inhibitors : Homeodomain Proteins, Tumor Suppressor Proteins.
- chemical , genetics : Homeodomain Proteins, Tumor Suppressor Proteins.
- chemical , metabolism : Homeodomain Proteins, Proto-Oncogene Proteins c-bcl-2, Tumor Suppressor Proteins, Wnt Proteins.
- chemical , toxicity : Chloroquine.
- drug effects : Apoptosis, Cell Proliferation.
- metabolism : Colonic Neoplasms, Neoplastic Stem Cells.
- mortality : Colonic Neoplasms.
- pathology : Colonic Neoplasms, Liver Neoplasms, Lung Neoplasms, Lymph Nodes.
- secondary : Liver Neoplasms, Lung Neoplasms.
- Animals, Cell Culture Techniques, Cell Line, Tumor, Humans, Lymphatic Metastasis, Mice, Mice, Inbred NOD, RNA Interference, Stress, Physiological, Wnt Signaling Pathway.
Abstract
The Wnt pathway is abnormally activated in the majority of colorectal cancers, and significant knowledge has been gained in understanding its role in tumor initiation. However, the mechanisms of metastatic outgrowth in colorectal cancer remain a major challenge. We report that autophagy-dependent metabolic adaptation and survival of metastatic colorectal cancer cells is regulated by the target of oncogenic Wnt signaling, homeobox transcription factor PROX1, expressed by a subpopulation of colon cancer progenitor/stem cells. We identify direct PROX1 target genes and show that repression of a pro-apoptotic member of the BCL2 family, BCL2L15, is important for survival of PROX1(+) cells under metabolic stress. PROX1 inactivation after the establishment of metastases prevented further growth of lesions. Furthermore, autophagy inhibition efficiently targeted metastatic PROX1(+) cells, suggesting a potential therapeutic approach. These data identify PROX1 as a key regulator of the transcriptional network contributing to metastases outgrowth in colorectal cancer.
DOI: 10.1016/j.celrep.2014.08.041
PubMed: 25242332
Affiliations:
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Le document en format XML
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Ivanov</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne 1066, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne 1066</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Zangger, Nadine" sort="Zangger, Nadine" uniqKey="Zangger N" first="Nadine" last="Zangger">Nadine Zangger</name><affiliation wicri:level="1"><nlm:affiliation>SIB Bioinformatics Core Facility, Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>SIB Bioinformatics Core Facility, Swiss Institute of Bioinformatics, Lausanne 1015</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Ceteci, Fatih" sort="Ceteci, Fatih" uniqKey="Ceteci F" first="Fatih" last="Ceteci">Fatih Ceteci</name><affiliation wicri:level="1"><nlm:affiliation>Cancer Research UK Beatson Institute, G61 1BD Glasgow, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Cancer Research UK Beatson Institute, G61 1BD Glasgow</wicri:regionArea><wicri:noRegion>G61 1BD Glasgow</wicri:noRegion></affiliation></author><author><name sortKey="Bernier Latmani, Jeremiah" sort="Bernier Latmani, Jeremiah" uniqKey="Bernier Latmani J" first="Jeremiah" last="Bernier-Latmani">Jeremiah Bernier-Latmani</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne 1066, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne 1066</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Milatos, Stavros" sort="Milatos, Stavros" uniqKey="Milatos S" first="Stavros" last="Milatos">Stavros Milatos</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne 1066, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne 1066</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Joseph, Jean Marc" sort="Joseph, Jean Marc" uniqKey="Joseph J" first="Jean-Marc" last="Joseph">Jean-Marc Joseph</name><affiliation wicri:level="1"><nlm:affiliation>Service de Chirurgie Pédiatrique, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne 1011, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Service de Chirurgie Pédiatrique, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne 1011</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Tercier, Stephane" sort="Tercier, Stephane" uniqKey="Tercier S" first="Stephane" last="Tercier">Stephane Tercier</name><affiliation wicri:level="1"><nlm:affiliation>Service de Chirurgie Pédiatrique, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne 1011, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Service de Chirurgie Pédiatrique, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne 1011</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Bouzourene, Hanifa" sort="Bouzourene, Hanifa" uniqKey="Bouzourene H" first="Hanifa" last="Bouzourene">Hanifa Bouzourene</name><affiliation wicri:level="1"><nlm:affiliation>UNISciences, University of Lausanne, UniLabs, Lausanne 1066, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>UNISciences, University of Lausanne, UniLabs, Lausanne 1066</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Bosman, Fredrik T" sort="Bosman, Fredrik T" uniqKey="Bosman F" first="Fredrik T" last="Bosman">Fredrik T. Bosman</name><affiliation wicri:level="1"><nlm:affiliation>Institut Universitaire de Pathologie, CHUV, Lausanne 1011, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Institut Universitaire de Pathologie, CHUV, Lausanne 1011</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Letovanec, Igor" sort="Letovanec, Igor" uniqKey="Letovanec I" first="Igor" last="Letovanec">Igor Letovanec</name><affiliation wicri:level="1"><nlm:affiliation>Institut Universitaire de Pathologie, CHUV, Lausanne 1011, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Institut Universitaire de Pathologie, CHUV, Lausanne 1011</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Marra, Giancarlo" sort="Marra, Giancarlo" uniqKey="Marra G" first="Giancarlo" last="Marra">Giancarlo Marra</name><affiliation wicri:level="4"><nlm:affiliation>Institute of Molecular Cancer Research, University of Zurich, Zurich 8057, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Molecular Cancer Research, University of Zurich, Zurich 8057</wicri:regionArea><orgName type="university">Université de Zurich</orgName><placeName><settlement type="city">Zurich</settlement><region nuts="3" type="region">Canton de Zurich</region></placeName></affiliation></author><author><name sortKey="Gonzalez, Michel" sort="Gonzalez, Michel" uniqKey="Gonzalez M" first="Michel" last="Gonzalez">Michel Gonzalez</name><affiliation wicri:level="1"><nlm:affiliation>Division of Thoracic Surgery, CHUV, Lausanne 1011, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Division of Thoracic Surgery, CHUV, Lausanne 1011</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Cammareri, Patrizia" sort="Cammareri, Patrizia" uniqKey="Cammareri P" first="Patrizia" last="Cammareri">Patrizia Cammareri</name><affiliation wicri:level="1"><nlm:affiliation>Cancer Research UK Beatson Institute, G61 1BD Glasgow, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Cancer Research UK Beatson Institute, G61 1BD Glasgow</wicri:regionArea><wicri:noRegion>G61 1BD Glasgow</wicri:noRegion></affiliation></author><author><name sortKey="Sansom, Owen J" sort="Sansom, Owen J" uniqKey="Sansom O" first="Owen J" last="Sansom">Owen J. Sansom</name><affiliation wicri:level="1"><nlm:affiliation>Cancer Research UK Beatson Institute, G61 1BD Glasgow, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Cancer Research UK Beatson Institute, G61 1BD Glasgow</wicri:regionArea><wicri:noRegion>G61 1BD Glasgow</wicri:noRegion></affiliation></author><author><name sortKey="Delorenzi, Mauro" sort="Delorenzi, Mauro" uniqKey="Delorenzi M" first="Mauro" last="Delorenzi">Mauro Delorenzi</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne 1066, Switzerland; SIB Bioinformatics Core Facility, Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland; Ludwig Center for Cancer Research, University of Lausanne, Lausanne 1066, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne 1066, Switzerland; SIB Bioinformatics Core Facility, Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland; Ludwig Center for Cancer Research, University of Lausanne, Lausanne 1066</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Petrova, Tatiana V" sort="Petrova, Tatiana V" uniqKey="Petrova T" first="Tatiana V" last="Petrova">Tatiana V. Petrova</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne 1066, Switzerland; Department of Biochemistry, University of Lausanne, Lausanne 1066, Switzerland; Swiss Institute for Cancer Research, EPFL, Lausanne 1015, Switzerland. Electronic address: tatiana.petrova@unil.ch.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne 1066, Switzerland; Department of Biochemistry, University of Lausanne, Lausanne 1066, Switzerland; Swiss Institute for Cancer Research, EPFL, Lausanne 1015</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:25242332</idno><idno type="pmid">25242332</idno><idno type="doi">10.1016/j.celrep.2014.08.041</idno><idno type="wicri:Area/PubMed/Corpus">000282</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000282</idno><idno type="wicri:Area/PubMed/Curation">000282</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000282</idno><idno type="wicri:Area/PubMed/Checkpoint">000279</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000279</idno><idno type="wicri:Area/Ncbi/Merge">000262</idno><idno type="wicri:Area/Ncbi/Curation">000262</idno><idno type="wicri:Area/Ncbi/Checkpoint">000262</idno><idno type="wicri:Area/Main/Merge">001012</idno><idno type="wicri:Area/Main/Curation">001011</idno><idno type="wicri:Area/Main/Exploration">001011</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">PROX1 promotes metabolic adaptation and fuels outgrowth of Wnt(high) metastatic colon cancer cells.</title><author><name sortKey="Ragusa, Simone" sort="Ragusa, Simone" uniqKey="Ragusa S" first="Simone" last="Ragusa">Simone Ragusa</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne 1066, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne 1066</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Cheng, Jianpin" sort="Cheng, Jianpin" uniqKey="Cheng J" first="Jianpin" last="Cheng">Jianpin Cheng</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne 1066, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne 1066</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Ivanov, Konstantin I" sort="Ivanov, Konstantin I" uniqKey="Ivanov K" first="Konstantin I" last="Ivanov">Konstantin I. Ivanov</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne 1066, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne 1066</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Zangger, Nadine" sort="Zangger, Nadine" uniqKey="Zangger N" first="Nadine" last="Zangger">Nadine Zangger</name><affiliation wicri:level="1"><nlm:affiliation>SIB Bioinformatics Core Facility, Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>SIB Bioinformatics Core Facility, Swiss Institute of Bioinformatics, Lausanne 1015</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Ceteci, Fatih" sort="Ceteci, Fatih" uniqKey="Ceteci F" first="Fatih" last="Ceteci">Fatih Ceteci</name><affiliation wicri:level="1"><nlm:affiliation>Cancer Research UK Beatson Institute, G61 1BD Glasgow, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Cancer Research UK Beatson Institute, G61 1BD Glasgow</wicri:regionArea><wicri:noRegion>G61 1BD Glasgow</wicri:noRegion></affiliation></author><author><name sortKey="Bernier Latmani, Jeremiah" sort="Bernier Latmani, Jeremiah" uniqKey="Bernier Latmani J" first="Jeremiah" last="Bernier-Latmani">Jeremiah Bernier-Latmani</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne 1066, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne 1066</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Milatos, Stavros" sort="Milatos, Stavros" uniqKey="Milatos S" first="Stavros" last="Milatos">Stavros Milatos</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne 1066, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne 1066</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Joseph, Jean Marc" sort="Joseph, Jean Marc" uniqKey="Joseph J" first="Jean-Marc" last="Joseph">Jean-Marc Joseph</name><affiliation wicri:level="1"><nlm:affiliation>Service de Chirurgie Pédiatrique, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne 1011, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Service de Chirurgie Pédiatrique, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne 1011</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Tercier, Stephane" sort="Tercier, Stephane" uniqKey="Tercier S" first="Stephane" last="Tercier">Stephane Tercier</name><affiliation wicri:level="1"><nlm:affiliation>Service de Chirurgie Pédiatrique, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne 1011, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Service de Chirurgie Pédiatrique, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne 1011</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Bouzourene, Hanifa" sort="Bouzourene, Hanifa" uniqKey="Bouzourene H" first="Hanifa" last="Bouzourene">Hanifa Bouzourene</name><affiliation wicri:level="1"><nlm:affiliation>UNISciences, University of Lausanne, UniLabs, Lausanne 1066, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>UNISciences, University of Lausanne, UniLabs, Lausanne 1066</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Bosman, Fredrik T" sort="Bosman, Fredrik T" uniqKey="Bosman F" first="Fredrik T" last="Bosman">Fredrik T. Bosman</name><affiliation wicri:level="1"><nlm:affiliation>Institut Universitaire de Pathologie, CHUV, Lausanne 1011, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Institut Universitaire de Pathologie, CHUV, Lausanne 1011</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Letovanec, Igor" sort="Letovanec, Igor" uniqKey="Letovanec I" first="Igor" last="Letovanec">Igor Letovanec</name><affiliation wicri:level="1"><nlm:affiliation>Institut Universitaire de Pathologie, CHUV, Lausanne 1011, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Institut Universitaire de Pathologie, CHUV, Lausanne 1011</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Marra, Giancarlo" sort="Marra, Giancarlo" uniqKey="Marra G" first="Giancarlo" last="Marra">Giancarlo Marra</name><affiliation wicri:level="4"><nlm:affiliation>Institute of Molecular Cancer Research, University of Zurich, Zurich 8057, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Molecular Cancer Research, University of Zurich, Zurich 8057</wicri:regionArea><orgName type="university">Université de Zurich</orgName><placeName><settlement type="city">Zurich</settlement><region nuts="3" type="region">Canton de Zurich</region></placeName></affiliation></author><author><name sortKey="Gonzalez, Michel" sort="Gonzalez, Michel" uniqKey="Gonzalez M" first="Michel" last="Gonzalez">Michel Gonzalez</name><affiliation wicri:level="1"><nlm:affiliation>Division of Thoracic Surgery, CHUV, Lausanne 1011, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Division of Thoracic Surgery, CHUV, Lausanne 1011</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Cammareri, Patrizia" sort="Cammareri, Patrizia" uniqKey="Cammareri P" first="Patrizia" last="Cammareri">Patrizia Cammareri</name><affiliation wicri:level="1"><nlm:affiliation>Cancer Research UK Beatson Institute, G61 1BD Glasgow, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Cancer Research UK Beatson Institute, G61 1BD Glasgow</wicri:regionArea><wicri:noRegion>G61 1BD Glasgow</wicri:noRegion></affiliation></author><author><name sortKey="Sansom, Owen J" sort="Sansom, Owen J" uniqKey="Sansom O" first="Owen J" last="Sansom">Owen J. Sansom</name><affiliation wicri:level="1"><nlm:affiliation>Cancer Research UK Beatson Institute, G61 1BD Glasgow, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Cancer Research UK Beatson Institute, G61 1BD Glasgow</wicri:regionArea><wicri:noRegion>G61 1BD Glasgow</wicri:noRegion></affiliation></author><author><name sortKey="Delorenzi, Mauro" sort="Delorenzi, Mauro" uniqKey="Delorenzi M" first="Mauro" last="Delorenzi">Mauro Delorenzi</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne 1066, Switzerland; SIB Bioinformatics Core Facility, Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland; Ludwig Center for Cancer Research, University of Lausanne, Lausanne 1066, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne 1066, Switzerland; SIB Bioinformatics Core Facility, Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland; Ludwig Center for Cancer Research, University of Lausanne, Lausanne 1066</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Petrova, Tatiana V" sort="Petrova, Tatiana V" uniqKey="Petrova T" first="Tatiana V" last="Petrova">Tatiana V. Petrova</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne 1066, Switzerland; Department of Biochemistry, University of Lausanne, Lausanne 1066, Switzerland; Swiss Institute for Cancer Research, EPFL, Lausanne 1015, Switzerland. Electronic address: tatiana.petrova@unil.ch.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne 1066, Switzerland; Department of Biochemistry, University of Lausanne, Lausanne 1066, Switzerland; Swiss Institute for Cancer Research, EPFL, Lausanne 1015</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author></analytic><series><title level="j">Cell reports</title><idno type="eISSN">2211-1247</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Apoptosis (drug effects)</term><term>Cell Culture Techniques</term><term>Cell Line, Tumor</term><term>Cell Proliferation (drug effects)</term><term>Chloroquine (toxicity)</term><term>Colonic Neoplasms (metabolism)</term><term>Colonic Neoplasms (mortality)</term><term>Colonic Neoplasms (pathology)</term><term>Homeodomain Proteins (antagonists & inhibitors)</term><term>Homeodomain Proteins (genetics)</term><term>Homeodomain Proteins (metabolism)</term><term>Humans</term><term>Liver Neoplasms (pathology)</term><term>Liver Neoplasms (secondary)</term><term>Lung Neoplasms (pathology)</term><term>Lung Neoplasms (secondary)</term><term>Lymph Nodes (pathology)</term><term>Lymphatic Metastasis</term><term>Mice</term><term>Mice, Inbred NOD</term><term>Neoplastic Stem Cells (metabolism)</term><term>Proto-Oncogene Proteins c-bcl-2 (metabolism)</term><term>RNA Interference</term><term>Stress, Physiological</term><term>Tumor Suppressor Proteins (antagonists & inhibitors)</term><term>Tumor Suppressor Proteins (genetics)</term><term>Tumor Suppressor Proteins (metabolism)</term><term>Wnt Proteins (metabolism)</term><term>Wnt Signaling Pathway</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Apoptose ()</term><term>Cellules souches tumorales (métabolisme)</term><term>Chloroquine (toxicité)</term><term>Humains</term><term>Interférence par ARN</term><term>Lignée cellulaire tumorale</term><term>Métastase lymphatique</term><term>Noeuds lymphatiques (anatomopathologie)</term><term>Prolifération cellulaire ()</term><term>Protéines de type Wingless (métabolisme)</term><term>Protéines proto-oncogènes c-bcl-2 (métabolisme)</term><term>Protéines suppresseurs de tumeurs (antagonistes et inhibiteurs)</term><term>Protéines suppresseurs de tumeurs (génétique)</term><term>Protéines suppresseurs de tumeurs (métabolisme)</term><term>Protéines à homéodomaine (antagonistes et inhibiteurs)</term><term>Protéines à homéodomaine (génétique)</term><term>Protéines à homéodomaine (métabolisme)</term><term>Souris</term><term>Souris de lignée NOD</term><term>Stress physiologique</term><term>Techniques de culture cellulaire</term><term>Tumeurs du côlon (anatomopathologie)</term><term>Tumeurs du côlon (mortalité)</term><term>Tumeurs du côlon (métabolisme)</term><term>Tumeurs du foie (anatomopathologie)</term><term>Tumeurs du foie (secondaire)</term><term>Tumeurs du poumon (anatomopathologie)</term><term>Tumeurs du poumon (secondaire)</term><term>Voie de signalisation Wnt</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Homeodomain Proteins</term><term>Tumor Suppressor Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Homeodomain Proteins</term><term>Tumor Suppressor Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Homeodomain Proteins</term><term>Proto-Oncogene Proteins c-bcl-2</term><term>Tumor Suppressor Proteins</term><term>Wnt Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="toxicity" xml:lang="en"><term>Chloroquine</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Noeuds lymphatiques</term><term>Tumeurs du côlon</term><term>Tumeurs du foie</term><term>Tumeurs du poumon</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Protéines suppresseurs de tumeurs</term><term>Protéines à homéodomaine</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Apoptosis</term><term>Cell Proliferation</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Protéines suppresseurs de tumeurs</term><term>Protéines à homéodomaine</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Colonic Neoplasms</term><term>Neoplastic Stem Cells</term></keywords><keywords scheme="MESH" qualifier="mortality" xml:lang="en"><term>Colonic Neoplasms</term></keywords><keywords scheme="MESH" qualifier="mortalité" xml:lang="fr"><term>Tumeurs du côlon</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cellules souches tumorales</term><term>Protéines de type Wingless</term><term>Protéines proto-oncogènes c-bcl-2</term><term>Protéines suppresseurs de tumeurs</term><term>Protéines à homéodomaine</term><term>Tumeurs du côlon</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Colonic Neoplasms</term><term>Liver Neoplasms</term><term>Lung Neoplasms</term><term>Lymph Nodes</term></keywords><keywords scheme="MESH" qualifier="secondaire" xml:lang="fr"><term>Tumeurs du foie</term><term>Tumeurs du poumon</term></keywords><keywords scheme="MESH" qualifier="secondary" xml:lang="en"><term>Liver Neoplasms</term><term>Lung Neoplasms</term></keywords><keywords scheme="MESH" qualifier="toxicité" xml:lang="fr"><term>Chloroquine</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Culture Techniques</term><term>Cell Line, Tumor</term><term>Humans</term><term>Lymphatic Metastasis</term><term>Mice</term><term>Mice, Inbred NOD</term><term>RNA Interference</term><term>Stress, Physiological</term><term>Wnt Signaling Pathway</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Apoptose</term><term>Humains</term><term>Interférence par ARN</term><term>Lignée cellulaire tumorale</term><term>Métastase lymphatique</term><term>Prolifération cellulaire</term><term>Souris</term><term>Souris de lignée NOD</term><term>Stress physiologique</term><term>Techniques de culture cellulaire</term><term>Voie de signalisation Wnt</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The Wnt pathway is abnormally activated in the majority of colorectal cancers, and significant knowledge has been gained in understanding its role in tumor initiation. However, the mechanisms of metastatic outgrowth in colorectal cancer remain a major challenge. We report that autophagy-dependent metabolic adaptation and survival of metastatic colorectal cancer cells is regulated by the target of oncogenic Wnt signaling, homeobox transcription factor PROX1, expressed by a subpopulation of colon cancer progenitor/stem cells. We identify direct PROX1 target genes and show that repression of a pro-apoptotic member of the BCL2 family, BCL2L15, is important for survival of PROX1(+) cells under metabolic stress. PROX1 inactivation after the establishment of metastases prevented further growth of lesions. Furthermore, autophagy inhibition efficiently targeted metastatic PROX1(+) cells, suggesting a potential therapeutic approach. These data identify PROX1 as a key regulator of the transcriptional network contributing to metastases outgrowth in colorectal cancer. </div></front></TEI><affiliations><list><country><li>Royaume-Uni</li><li>Suisse</li></country><region><li>Canton de Vaud</li><li>Canton de Zurich</li></region><settlement><li>Lausanne</li><li>Zurich</li></settlement><orgName><li>Université de Zurich</li></orgName></list><tree><country name="Suisse"><region name="Canton de Vaud"><name sortKey="Ragusa, Simone" sort="Ragusa, Simone" uniqKey="Ragusa S" first="Simone" last="Ragusa">Simone Ragusa</name></region><name sortKey="Bernier Latmani, Jeremiah" sort="Bernier Latmani, Jeremiah" uniqKey="Bernier Latmani J" first="Jeremiah" last="Bernier-Latmani">Jeremiah Bernier-Latmani</name><name sortKey="Bosman, Fredrik T" sort="Bosman, Fredrik T" uniqKey="Bosman F" first="Fredrik T" last="Bosman">Fredrik T. Bosman</name><name sortKey="Bouzourene, Hanifa" sort="Bouzourene, Hanifa" uniqKey="Bouzourene H" first="Hanifa" last="Bouzourene">Hanifa Bouzourene</name><name sortKey="Cheng, Jianpin" sort="Cheng, Jianpin" uniqKey="Cheng J" first="Jianpin" last="Cheng">Jianpin Cheng</name><name sortKey="Delorenzi, Mauro" sort="Delorenzi, Mauro" uniqKey="Delorenzi M" first="Mauro" last="Delorenzi">Mauro Delorenzi</name><name sortKey="Gonzalez, Michel" sort="Gonzalez, Michel" uniqKey="Gonzalez M" first="Michel" last="Gonzalez">Michel Gonzalez</name><name sortKey="Ivanov, Konstantin I" sort="Ivanov, Konstantin I" uniqKey="Ivanov K" first="Konstantin I" last="Ivanov">Konstantin I. Ivanov</name><name sortKey="Joseph, Jean Marc" sort="Joseph, Jean Marc" uniqKey="Joseph J" first="Jean-Marc" last="Joseph">Jean-Marc Joseph</name><name sortKey="Letovanec, Igor" sort="Letovanec, Igor" uniqKey="Letovanec I" first="Igor" last="Letovanec">Igor Letovanec</name><name sortKey="Marra, Giancarlo" sort="Marra, Giancarlo" uniqKey="Marra G" first="Giancarlo" last="Marra">Giancarlo Marra</name><name sortKey="Milatos, Stavros" sort="Milatos, Stavros" uniqKey="Milatos S" first="Stavros" last="Milatos">Stavros Milatos</name><name sortKey="Petrova, Tatiana V" sort="Petrova, Tatiana V" uniqKey="Petrova T" first="Tatiana V" last="Petrova">Tatiana V. Petrova</name><name sortKey="Tercier, Stephane" sort="Tercier, Stephane" uniqKey="Tercier S" first="Stephane" last="Tercier">Stephane Tercier</name><name sortKey="Zangger, Nadine" sort="Zangger, Nadine" uniqKey="Zangger N" first="Nadine" last="Zangger">Nadine Zangger</name></country><country name="Royaume-Uni"><noRegion><name sortKey="Ceteci, Fatih" sort="Ceteci, Fatih" uniqKey="Ceteci F" first="Fatih" last="Ceteci">Fatih Ceteci</name></noRegion><name sortKey="Cammareri, Patrizia" sort="Cammareri, Patrizia" uniqKey="Cammareri P" first="Patrizia" last="Cammareri">Patrizia Cammareri</name><name sortKey="Sansom, Owen J" sort="Sansom, Owen J" uniqKey="Sansom O" first="Owen J" last="Sansom">Owen J. Sansom</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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