Metastatic Colonization Requires the Repression of the Epithelial-Mesenchymal Transition Inducer Prrx1
The epithelial-mesenchymal transition (EMT) is required in the embryo for the formation of tissues for which cells originate far from their final destination. Carcinoma cells hijack this program for tumor dissemination. The relevance of the EMT in cancer is still debated because it is unclear how th...
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Veröffentlicht in: | Cancer cell 2012-12, Vol.22 (6), p.709-724 |
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creator | Ocaña, Oscar H. Córcoles, Rebeca Fabra, Ángels Moreno-Bueno, Gema Acloque, Hervé Vega, Sonia Barrallo-Gimeno, Alejandro Cano, Amparo Nieto, M. Angela |
description | The epithelial-mesenchymal transition (EMT) is required in the embryo for the formation of tissues for which cells originate far from their final destination. Carcinoma cells hijack this program for tumor dissemination. The relevance of the EMT in cancer is still debated because it is unclear how these migratory cells colonize distant tissues to form macrometastases. We show that the homeobox factor Prrx1 is an EMT inducer conferring migratory and invasive properties. The loss of Prrx1 is required for cancer cells to metastasize in vivo, which revert to the epithelial phenotype concomitant with the acquisition of stem cell properties. Thus, unlike the classical EMT transcription factors, Prrx1 uncouples EMT and stemness, and is a biomarker associated with patient survival and lack of metastasis.
► Prrx1 is an epithelial-mesenchymal transition inducer in embryos and cancer cells ► Prrx1 cooperates with Twist1 for invasion in embryonic and cancer cells ► Prrx1 loss reverts EMT & induces stemness, both required for metastatic colonization ► High Prrx1 expression associates with good prognosis |
doi_str_mv | 10.1016/j.ccr.2012.10.012 |
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► Prrx1 is an epithelial-mesenchymal transition inducer in embryos and cancer cells ► Prrx1 cooperates with Twist1 for invasion in embryonic and cancer cells ► Prrx1 loss reverts EMT & induces stemness, both required for metastatic colonization ► High Prrx1 expression associates with good prognosis</description><identifier>ISSN: 1535-6108</identifier><identifier>EISSN: 1878-3686</identifier><identifier>DOI: 10.1016/j.ccr.2012.10.012</identifier><identifier>PMID: 23201163</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Cancer ; Cell Behavior ; Cell Line, Tumor ; Cell Movement - genetics ; Cell Movement - physiology ; Cellular Biology ; Development Biology ; Embryology and Organogenesis ; Epithelial Cells - metabolism ; Epithelial Cells - pathology ; Epithelial-Mesenchymal Transition - genetics ; Epithelial-Mesenchymal Transition - physiology ; Female ; Homeodomain Proteins - genetics ; Homeodomain Proteins - metabolism ; Homeodomain Proteins - physiology ; Humans ; Life Sciences ; MCF-7 Cells ; Middle Aged ; Neoplasm Metastasis ; Prognosis ; Retrospective Studies ; Stem Cells - metabolism ; Stem Cells - pathology</subject><ispartof>Cancer cell, 2012-12, Vol.22 (6), p.709-724</ispartof><rights>2012 Elsevier Inc.</rights><rights>Copyright © 2012 Elsevier Inc. All rights reserved.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c496t-98a7b1f9e1ea9fca8b0f5c3a038dc09e4ea399d4217d6eb7644842c0fe15672f3</citedby><cites>FETCH-LOGICAL-c496t-98a7b1f9e1ea9fca8b0f5c3a038dc09e4ea399d4217d6eb7644842c0fe15672f3</cites><orcidid>0000-0003-4761-1055</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1535610812004424$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23201163$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.inrae.fr/hal-02912713$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Ocaña, Oscar H.</creatorcontrib><creatorcontrib>Córcoles, Rebeca</creatorcontrib><creatorcontrib>Fabra, Ángels</creatorcontrib><creatorcontrib>Moreno-Bueno, Gema</creatorcontrib><creatorcontrib>Acloque, Hervé</creatorcontrib><creatorcontrib>Vega, Sonia</creatorcontrib><creatorcontrib>Barrallo-Gimeno, Alejandro</creatorcontrib><creatorcontrib>Cano, Amparo</creatorcontrib><creatorcontrib>Nieto, M. Angela</creatorcontrib><title>Metastatic Colonization Requires the Repression of the Epithelial-Mesenchymal Transition Inducer Prrx1</title><title>Cancer cell</title><addtitle>Cancer Cell</addtitle><description>The epithelial-mesenchymal transition (EMT) is required in the embryo for the formation of tissues for which cells originate far from their final destination. Carcinoma cells hijack this program for tumor dissemination. The relevance of the EMT in cancer is still debated because it is unclear how these migratory cells colonize distant tissues to form macrometastases. We show that the homeobox factor Prrx1 is an EMT inducer conferring migratory and invasive properties. The loss of Prrx1 is required for cancer cells to metastasize in vivo, which revert to the epithelial phenotype concomitant with the acquisition of stem cell properties. Thus, unlike the classical EMT transcription factors, Prrx1 uncouples EMT and stemness, and is a biomarker associated with patient survival and lack of metastasis.
► Prrx1 is an epithelial-mesenchymal transition inducer in embryos and cancer cells ► Prrx1 cooperates with Twist1 for invasion in embryonic and cancer cells ► Prrx1 loss reverts EMT & induces stemness, both required for metastatic colonization ► High Prrx1 expression associates with good prognosis</description><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>Cancer</subject><subject>Cell Behavior</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - genetics</subject><subject>Cell Movement - physiology</subject><subject>Cellular Biology</subject><subject>Development Biology</subject><subject>Embryology and Organogenesis</subject><subject>Epithelial Cells - metabolism</subject><subject>Epithelial Cells - pathology</subject><subject>Epithelial-Mesenchymal Transition - genetics</subject><subject>Epithelial-Mesenchymal Transition - physiology</subject><subject>Female</subject><subject>Homeodomain Proteins - genetics</subject><subject>Homeodomain Proteins - metabolism</subject><subject>Homeodomain Proteins - physiology</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>MCF-7 Cells</subject><subject>Middle Aged</subject><subject>Neoplasm Metastasis</subject><subject>Prognosis</subject><subject>Retrospective Studies</subject><subject>Stem Cells - metabolism</subject><subject>Stem Cells - pathology</subject><issn>1535-6108</issn><issn>1878-3686</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UU1v1DAUtBCoLaU_gAvKEQ5Z_OLEscWpWvVL2gqEytnyOs9ar7Lx1k4q2l_fl27pkdO8N5qZwwxjn4EvgIP8vl04lxYVh4r-BcE7dgKqVaWQSr6nuxFNKYGrY_Yx5y0nD7T6iB1XgkwgxQnztzjaPNoxuGIZ-ziEJ7rjUPzG-ykkzMW4QXr2dOaZj_6FudgHgj7YvrzFjIPbPO5sX9wlO-TwEnAzdJPDVPxK6S98Yh-87TOeveIp-3N5cbe8Llc_r26W56vS1VqOpVa2XYPXCGi1d1atuW-csFyoznGNNVqhdVdX0HYS162sa1VXjnuERraVF6fs2yF3Y3uzT2Fn06OJNpjr85WZOV5pqFoQD0DarwftPsX7CfNodiE77Hs7YJyygUpoLrlqWpLCQepSzDmhf8sGbuYpzNbQFGaeYqYIyPPlNX5a77B7c_zrngQ_DgKkQh4CJpNdoCaxo97daLoY_hP_DIfAmdw</recordid><startdate>20121211</startdate><enddate>20121211</enddate><creator>Ocaña, Oscar H.</creator><creator>Córcoles, Rebeca</creator><creator>Fabra, Ángels</creator><creator>Moreno-Bueno, Gema</creator><creator>Acloque, Hervé</creator><creator>Vega, Sonia</creator><creator>Barrallo-Gimeno, Alejandro</creator><creator>Cano, Amparo</creator><creator>Nieto, M. Angela</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0003-4761-1055</orcidid></search><sort><creationdate>20121211</creationdate><title>Metastatic Colonization Requires the Repression of the Epithelial-Mesenchymal Transition Inducer Prrx1</title><author>Ocaña, Oscar H. ; Córcoles, Rebeca ; Fabra, Ángels ; Moreno-Bueno, Gema ; Acloque, Hervé ; Vega, Sonia ; Barrallo-Gimeno, Alejandro ; Cano, Amparo ; Nieto, M. Angela</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c496t-98a7b1f9e1ea9fca8b0f5c3a038dc09e4ea399d4217d6eb7644842c0fe15672f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - metabolism</topic><topic>Breast Neoplasms - pathology</topic><topic>Cancer</topic><topic>Cell Behavior</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - genetics</topic><topic>Cell Movement - physiology</topic><topic>Cellular Biology</topic><topic>Development Biology</topic><topic>Embryology and Organogenesis</topic><topic>Epithelial Cells - metabolism</topic><topic>Epithelial Cells - pathology</topic><topic>Epithelial-Mesenchymal Transition - genetics</topic><topic>Epithelial-Mesenchymal Transition - physiology</topic><topic>Female</topic><topic>Homeodomain Proteins - genetics</topic><topic>Homeodomain Proteins - metabolism</topic><topic>Homeodomain Proteins - physiology</topic><topic>Humans</topic><topic>Life Sciences</topic><topic>MCF-7 Cells</topic><topic>Middle Aged</topic><topic>Neoplasm Metastasis</topic><topic>Prognosis</topic><topic>Retrospective Studies</topic><topic>Stem Cells - metabolism</topic><topic>Stem Cells - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ocaña, Oscar H.</creatorcontrib><creatorcontrib>Córcoles, Rebeca</creatorcontrib><creatorcontrib>Fabra, Ángels</creatorcontrib><creatorcontrib>Moreno-Bueno, Gema</creatorcontrib><creatorcontrib>Acloque, Hervé</creatorcontrib><creatorcontrib>Vega, Sonia</creatorcontrib><creatorcontrib>Barrallo-Gimeno, Alejandro</creatorcontrib><creatorcontrib>Cano, Amparo</creatorcontrib><creatorcontrib>Nieto, M. Angela</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Cancer cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ocaña, Oscar H.</au><au>Córcoles, Rebeca</au><au>Fabra, Ángels</au><au>Moreno-Bueno, Gema</au><au>Acloque, Hervé</au><au>Vega, Sonia</au><au>Barrallo-Gimeno, Alejandro</au><au>Cano, Amparo</au><au>Nieto, M. Angela</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Metastatic Colonization Requires the Repression of the Epithelial-Mesenchymal Transition Inducer Prrx1</atitle><jtitle>Cancer cell</jtitle><addtitle>Cancer Cell</addtitle><date>2012-12-11</date><risdate>2012</risdate><volume>22</volume><issue>6</issue><spage>709</spage><epage>724</epage><pages>709-724</pages><issn>1535-6108</issn><eissn>1878-3686</eissn><abstract>The epithelial-mesenchymal transition (EMT) is required in the embryo for the formation of tissues for which cells originate far from their final destination. Carcinoma cells hijack this program for tumor dissemination. The relevance of the EMT in cancer is still debated because it is unclear how these migratory cells colonize distant tissues to form macrometastases. We show that the homeobox factor Prrx1 is an EMT inducer conferring migratory and invasive properties. The loss of Prrx1 is required for cancer cells to metastasize in vivo, which revert to the epithelial phenotype concomitant with the acquisition of stem cell properties. Thus, unlike the classical EMT transcription factors, Prrx1 uncouples EMT and stemness, and is a biomarker associated with patient survival and lack of metastasis.
► Prrx1 is an epithelial-mesenchymal transition inducer in embryos and cancer cells ► Prrx1 cooperates with Twist1 for invasion in embryonic and cancer cells ► Prrx1 loss reverts EMT & induces stemness, both required for metastatic colonization ► High Prrx1 expression associates with good prognosis</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>23201163</pmid><doi>10.1016/j.ccr.2012.10.012</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0003-4761-1055</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Breast Neoplasms - genetics Breast Neoplasms - metabolism Breast Neoplasms - pathology Cancer Cell Behavior Cell Line, Tumor Cell Movement - genetics Cell Movement - physiology Cellular Biology Development Biology Embryology and Organogenesis Epithelial Cells - metabolism Epithelial Cells - pathology Epithelial-Mesenchymal Transition - genetics Epithelial-Mesenchymal Transition - physiology Female Homeodomain Proteins - genetics Homeodomain Proteins - metabolism Homeodomain Proteins - physiology Humans Life Sciences MCF-7 Cells Middle Aged Neoplasm Metastasis Prognosis Retrospective Studies Stem Cells - metabolism Stem Cells - pathology |
title | Metastatic Colonization Requires the Repression of the Epithelial-Mesenchymal Transition Inducer Prrx1 |
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