{"id":1752,"date":"2018-04-09T11:25:42","date_gmt":"2018-04-09T15:25:42","guid":{"rendered":"https:\/\/www.bumc.bu.edu\/cancercenter\/?p=1752"},"modified":"2018-04-09T11:26:55","modified_gmt":"2018-04-09T15:26:55","slug":"bet-proteins-exhibit-transcriptional-and-functional-opposition-in-the-epithelial-to-mesenchymal-transition","status":"publish","type":"post","link":"https:\/\/www.bumc.bu.edu\/cancercenter\/2018\/04\/09\/bet-proteins-exhibit-transcriptional-and-functional-opposition-in-the-epithelial-to-mesenchymal-transition\/","title":{"rendered":"BET Proteins Exhibit Transcriptional and Functional Opposition in the Epithelial-to-Mesenchymal Transition"},"content":{"rendered":"<p>Published April 2018<br \/>\nProvided by:\u00a0American Association for Cancer Research Publications | Source: <a href=\"http:\/\/mcr.aacrjournals.org\/content\/16\/4\/580\">Molecular Cancer Research<\/a><\/p>\n<div class=\"highwire-cite-authors\"><span class=\"highwire-citation-authors\"><span class=\"highwire-citation-authors\"><span class=\"highwire-citation-author first has-tooltip hasTooltip\" aria-describedby=\"qtip-1\" data-hasqtip=\"1\" data-delta=\"0\"><span class=\"nlm-given-names\">Guillaume P.<\/span> <span class=\"nlm-surname\">Andrieu<\/span><\/span> and <span class=\"highwire-citation-author has-tooltip hasTooltip\" aria-describedby=\"qtip-0\" data-hasqtip=\"0\" data-delta=\"1\"><span class=\"nlm-given-names\">Gerald V.<\/span> <span class=\"nlm-surname\">Denis<br \/>\n<\/span><\/span><\/span><\/span><span class=\"highwire-cite-metadata-doi highwire-cite-metadata\"><span class=\"metadata-label\"><b>DOI:<\/b><\/span> 10.1158\/1541-7786.MCR-17-0568<\/p>\n<p><\/span><strong>Abstract<\/strong><\/div>\n<div class=\"highwire-cite-authors\">\n<div class=\"section abstract\" id=\"abstract-1\">\n<p id=\"p-2\">Transcriptional programs in embryogenesis and cancer, such as the epithelial-to-mesenchymal transition (EMT), ensure cellular plasticity, an essential feature of carcinoma progression. As effectors of signal transduction, the bromodomain and extraterminal (BET) proteins are well suited to support plasticity because they function as co-activators or co-repressors of mammalian transcriptomes. Here, using both hormone-sensitive and triple-negative breast cancer (TNBC) model systems, we systematically altered EMT transcriptional profiles by manipulating individual BET proteins and found that BRD2 positively regulates EMT, whereas BRD3 and BRD4 repress this program. Knockdown of individual BET proteins revealed independent transcriptional networks that differed from each other and from the small-molecule pan-BET inhibitor JQ1, which previously had been misleadingly asserted to be BRD4-selective. Available small-molecule pan-BET inhibitors, proposed as antiproliferative agents in cancer clinical trials, obscure these biological differences. Transcriptional profiling reveals that individual BET proteins, inhibited separately, engage in and control EMT through unique processes.<\/p>\n<p id=\"p-3\"><strong>Visual Overview:<\/strong> <a class=\"in-nw\" href=\"http:\/\/mcr.aacrjournals.org\/content\/molcanres\/16\/4\/580\/F1.large.jpg\">http:\/\/mcr.aacrjournals.org\/content\/molcanres\/16\/4\/580\/F1.large.jpg<\/a>. <em>Mol Cancer Res; 16(4); 580\u20136. \u00a92018 AACR<\/em>.<\/p>\n<\/div>\n<div class=\"notes\">\n<p class=\"comment-on\" id=\"p-5\">This article is featured in Highlights of This Issue, <a href=\"http:\/\/mcr.aacrjournals.org\/lookup\/volpage\/16\/565?iss=4\">p. 565<\/a><\/p>\n<\/div>\n<\/div>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Published April 2018 Provided by:\u00a0American Association for Cancer Research Publications | Source: Molecular Cancer Research Guillaume P. Andrieu and Gerald V. Denis DOI: 10.1158\/1541-7786.MCR-17-0568 Abstract Transcriptional programs in embryogenesis and cancer, such as the epithelial-to-mesenchymal transition (EMT), ensure cellular plasticity, an essential feature of carcinoma progression. As effectors of signal transduction, the bromodomain and extraterminal [&hellip;]<\/p>\n","protected":false},"author":11679,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[1667,1662,1665],"tags":[],"_links":{"self":[{"href":"https:\/\/www.bumc.bu.edu\/cancercenter\/wp-json\/wp\/v2\/posts\/1752"}],"collection":[{"href":"https:\/\/www.bumc.bu.edu\/cancercenter\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.bumc.bu.edu\/cancercenter\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/cancercenter\/wp-json\/wp\/v2\/users\/11679"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/cancercenter\/wp-json\/wp\/v2\/comments?post=1752"}],"version-history":[{"count":4,"href":"https:\/\/www.bumc.bu.edu\/cancercenter\/wp-json\/wp\/v2\/posts\/1752\/revisions"}],"predecessor-version":[{"id":1756,"href":"https:\/\/www.bumc.bu.edu\/cancercenter\/wp-json\/wp\/v2\/posts\/1752\/revisions\/1756"}],"wp:attachment":[{"href":"https:\/\/www.bumc.bu.edu\/cancercenter\/wp-json\/wp\/v2\/media?parent=1752"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/cancercenter\/wp-json\/wp\/v2\/categories?post=1752"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/cancercenter\/wp-json\/wp\/v2\/tags?post=1752"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}