{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T14:06:49Z","timestamp":1779026809796,"version":"3.51.4"},"reference-count":21,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,1,21]],"date-time":"2017-01-21T00:00:00Z","timestamp":1484956800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,1,21]],"date-time":"2017-01-21T00:00:00Z","timestamp":1484956800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000325","name":"Wellbeing of Women","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000325","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["ELS203"],"award-info":[{"award-number":["ELS203"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2017,2]]},"abstract":"Abstract<\/jats:title>\n \n Urocortin (\n UCN<\/jats:styled-content>\n 1) peptide shares structural and functional homology with corticotropin\u2010releasing factor (\n CRF<\/jats:styled-content>\n ).\n UCN<\/jats:styled-content>\n 1 is significantly reduced in endometrial adenocarcinoma compared to healthy controls. However, there are no data which evaluate the effects of\n UCN<\/jats:styled-content>\n 1 in the endometrium, or how it is modulated. We used proliferation and transwell assays to determine the effect of\n UCN<\/jats:styled-content>\n 1 on the proliferation and migration of Ishikawa and\n HEC<\/jats:styled-content>\n 1A cells. We also determined the expression levels of\n UCN<\/jats:styled-content>\n 1 and its receptors produced by estrogen receptor agonists, and the effect of\n UCN<\/jats:styled-content>\n 1 on estrogen receptor expression, using quantitative polymerase chain reaction.\n UCN<\/jats:styled-content>\n 1 suppressed migration of endometrial cancer cells in vitro. This effect appears to be specific to\n CRF<\/jats:styled-content>\n receptor 2 (\n CRFR<\/jats:styled-content>\n 2), as selective antagonism of\n CRFR<\/jats:styled-content>\n 2 but not\n CRFR<\/jats:styled-content>\n 1 completely eliminated suppression of migration. Activation of\n ERA<\/jats:styled-content>\n reduced\n UCN<\/jats:styled-content>\n 1 expression, but only had a small effect on the expression of\n CRFR<\/jats:styled-content>\n 1. However, expression of\n CRFR<\/jats:styled-content>\n 2 was more notably reduced at both the m\n RNA<\/jats:styled-content>\n and protein levels by activation of\n ERB<\/jats:styled-content>\n .\n UCN<\/jats:styled-content>\n 1 in turn reduced both\n ERA<\/jats:styled-content>\n and\n ERB<\/jats:styled-content>\n expression, as assessed by real\u2010time quantitative\n PCR<\/jats:styled-content>\n . We demonstrate that\n UCN<\/jats:styled-content>\n 1 significantly suppresses the migration of endometrial cancer cells but has no effect on their proliferation. Thus, loss of\n UCN<\/jats:styled-content>\n 1 in endometrial cancer may promote invasion and metastatic spread. There is a complex relationship between the\n UCN<\/jats:styled-content>\n 1 system and estrogen receptors, which may provide insights into endometrial carcinogenesis, a disease known to be driven by estrogen excess.\n <\/jats:p>","DOI":"10.1002\/cam4.967","type":"journal-article","created":{"date-parts":[[2017,1,21]],"date-time":"2017-01-21T00:10:07Z","timestamp":1484957407000},"page":"408-415","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Urocortin suppresses endometrial cancer cell migration via CRFR2 and its system components are differentially modulated by estrogen"],"prefix":"10.1002","volume":"6","author":[{"given":"Gemma L.","family":"Owens","sequence":"first","affiliation":[{"name":"Division of Molecular & Clinical Cancer Sciences School of Medical Sciences Faculty of Biology Medicine & Health Manchester Cancer Research Centre University of Manchester Wilmslow Road Manchester M20 4QL United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin M.","family":"Lawrence","sequence":"additional","affiliation":[{"name":"Division of Molecular & Clinical Cancer Sciences School of Medical Sciences Faculty of Biology Medicine & Health Manchester Cancer Research Centre University of Manchester Wilmslow Road Manchester M20 4QL United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom R.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Division of Molecular & Clinical Cancer Sciences School of Medical Sciences Faculty of Biology Medicine & Health Manchester Cancer Research Centre University of Manchester Wilmslow Road Manchester M20 4QL United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma J.","family":"Crosbie","sequence":"additional","affiliation":[{"name":"Division of Molecular & Clinical Cancer Sciences School of Medical Sciences Faculty of Biology Medicine & Health St Mary's Hospital University of Manchester Oxford Road Manchester M13 9WL United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Berna S.","family":"Sayan","sequence":"additional","affiliation":[{"name":"Division of Molecular & Clinical Cancer Sciences School of Medical Sciences Faculty of Biology Medicine & Health Manchester Cancer Research Centre University of Manchester Wilmslow Road Manchester M20 4QL United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry C.","family":"Kitchener","sequence":"additional","affiliation":[{"name":"Division of Molecular & Clinical Cancer Sciences School of Medical Sciences Faculty of Biology Medicine & Health St Mary's Hospital University of Manchester Oxford Road Manchester M13 9WL United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul A.","family":"Townsend","sequence":"additional","affiliation":[{"name":"Division of Molecular & Clinical Cancer Sciences School of Medical Sciences Faculty of Biology Medicine & Health Manchester Cancer Research Centre University of Manchester Wilmslow Road Manchester M20 4QL United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,1,21]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00130-0"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-04-0871"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/378287a0"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.143.3.8694"},{"key":"e_1_2_6_6_1","first-page":"375","article-title":"Corticotropin\u2010releasing hormone receptor\u20101 in human endometrial cancer","volume":"15","author":"Graziani G.","year":"2006","journal-title":"Oncol. 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