{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:36:30Z","timestamp":1789389390907,"version":"build-2803163510"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2011,3,14]],"date-time":"2011-03-14T00:00:00Z","timestamp":1300060800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Cancer Research UK China Fellowship"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2011,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Polyomavirus enhancer activator 3 protein (Pea3), also known as <jats:italic>ETV4<\/jats:italic>, is a member of the Ets\u2010transcription factor family, which promotes metastatic progression in various types of solid cancer. Pea3\u2010driven epithelial\u2010mesenchymal transition (EMT) has been described in lung and ovarian cancers. The mechanisms of Pea3\u2010induced EMT, however, are largely unknown. Here we show that Pea3 overexpression promotes EMT in human breast epithelial cells through transactivation of Snail (<jats:italic>SNAI1<\/jats:italic>), an activator of EMT. Pea3 binds to the human Snail promoter through the two proximal Pea3 binding sites and enhances Snail expression. In addition, knockdown of Pea3 in invasive breast cancer cells results in down\u2010regulation of Snail, partial reversal of EMT, and reduced invasiveness <jats:italic>in vitro<\/jats:italic>. Moreover, knockdown of Snail partially rescues the phenotype induced by Pea3 overexpression, suggesting that Snail is one of the mediators bridging Pea3 and EMT, and thereby metastatic progression of the cancer cells. In four breast cancer patient cohorts whose microarray and survival data were obtained from the Gene Expression Omnibus database, Pea3 and Snail expression are significantly correlated with each other and with overall survival of breast cancer patients. We further demonstrate that nuclear localization of Pea3 is associated with Snail expression in breast cancer cell lines and is an independent predictor of overall survival in a Chinese breast cancer patient cohort. In conclusion, our results suggest that Pea3 may be an important prognostic marker and a therapeutic target for metastatic progression of human breast cancer. Copyright \u00a9 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.2859","type":"journal-article","created":{"date-parts":[[2011,1,17]],"date-time":"2011-01-17T10:10:24Z","timestamp":1295259024000},"page":"78-89","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Polyomavirus enhancer activator 3 protein promotes breast cancer metastatic progression through Snail\u2010induced epithelial\u2013mesenchymal transition"],"prefix":"10.1002","volume":"224","author":[{"given":"Hiu\u2010Fung","family":"Yuen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuen\u2010Kwong","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Grills","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cian M","family":"McCrudden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vignesh","family":"Gunasekharan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanzhong","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley San\u2010Yu","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terence R","family":"Lappin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwok\u2010Wah","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean A","family":"Fennell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ui\u2010Soon","family":"Khoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick G","family":"Johnston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"El\u2010Tanani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,3,14]]},"reference":[{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.20006"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1677\/ERC-09-0012"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.11.007"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI39104"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2008.05.009"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm757"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-3850"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.06.006"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2007.02665.x"},{"key":"e_1_2_7_12_2","first-page":"1613","article-title":"The SLUG zinc\u2010finger protein represses E\u2010cadherin in breast cancer","volume":"62","author":"Hajra KM","year":"2002","journal-title":"Cancer Res"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2005.07.009"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1006\/bmme.1997.2605"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.1410"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1387"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgh011"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgp129"},{"key":"e_1_2_7_19_2","first-page":"1667","article-title":"PEA3 transactivates vimentin promoter in mammary epithelial and tumor cells","volume":"13","author":"Chen JH","year":"1996","journal-title":"Oncogene"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-2902"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1593\/neo.09942"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-4389"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2131"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01907"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-2318"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2009.03.017"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/72294"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.325"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgn105"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-3785"},{"key":"e_1_2_7_31_2","unstructured":"RDevelopmentCoreTeam.R: A language and environment for statistical computing [Internet]. Available from:http:\/\/www.R\u2010project.orgAccessed 16th December 2010."},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2004-5-10-r80"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1530509100"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6605480"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-0494"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.1159\/000228908"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6446(02)02562-X"},{"key":"e_1_2_7_38_2","doi-asserted-by":"publisher","DOI":"10.1134\/S0006297907130032"},{"key":"e_1_2_7_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2006.10.008"},{"key":"e_1_2_7_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21223"},{"key":"e_1_2_7_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00579-08"},{"key":"e_1_2_7_42_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008854"},{"key":"e_1_2_7_43_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M311131200"},{"key":"e_1_2_7_44_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-0955"},{"key":"e_1_2_7_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.494"},{"key":"e_1_2_7_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210546"},{"key":"e_1_2_7_47_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-0011"},{"key":"e_1_2_7_48_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-2926"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.2859","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.2859","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.2859","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T13:10:45Z","timestamp":1761052245000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.2859"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,3,14]]},"references-count":46,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2011,5]]}},"alternative-id":["10.1002\/path.2859"],"URL":"https:\/\/doi.org\/10.1002\/path.2859","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,3,14]]},"assertion":[{"value":"2010-08-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-01-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-03-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}