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We demonstrate that, even though snail family transcriptional repressor 2 (\n                    <jats:italic>SNAI2<\/jats:italic>\n                    ) is frequently amplified in prostate cancer, it is epigenetically silenced in this disease, with dynamic changes in\n                    <jats:italic>SNAI2<\/jats:italic>\n                    levels showing distinct clinical relevance. Integrative clinical data from 18 prostate cancer cohorts and experimental evidence showed that gene fusion between transmembrane serine protease 2 (\n                    <jats:italic>TMPRSS2<\/jats:italic>\n                    ) and ETS transcription factor ERG (\n                    <jats:italic>ERG<\/jats:italic>\n                    ) (\n                    <jats:italic>TMPRSS2\u2013ERG<\/jats:italic>\n                    fusion) is involved in the silencing of\n                    <jats:italic>SNAI2<\/jats:italic>\n                    . We created a silencer score to evaluate epigenetic repression of\n                    <jats:italic>SNAI2<\/jats:italic>\n                    , which can be reversed by treatment with DNA methyltransferase inhibitors and histone deacetylase inhibitors. Silencing of\n                    <jats:italic>SNAI2<\/jats:italic>\n                    facilitated tumor cell proliferation and luminal differentiation. Furthermore,\n                    <jats:italic>SNAI2<\/jats:italic>\n                    has a major influence on the tumor microenvironment by reactivating tumor stroma and creating an immunosuppressive microenvironment in prostate cancer. Importantly,\n                    <jats:italic>SNAI2<\/jats:italic>\n                    expression levels in part determine sensitivity to the cancer drugs dasatinib and panobinostat. For the first time, we defined the distinct clinical relevance of\n                    <jats:italic>SNAI2<\/jats:italic>\n                    expression at different disease stages. We elucidated how epigenetic silencing of\n                    <jats:italic>SNAI2<\/jats:italic>\n                    controls the dynamic changes of\n                    <jats:italic>SNAI2<\/jats:italic>\n                    expression that are essential for tumor initiation and progression and discovered that restoring\n                    <jats:italic>SNAI2<\/jats:italic>\n                    expression by treatment with panobinostat enhances dasatinib sensitivity, indicating a new therapeutic strategy for prostate cancer.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.13140","type":"journal-article","created":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T07:27:27Z","timestamp":1637220447000},"page":"2451-2469","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Dynamic expression of SNAI2 in prostate cancer predicts tumor progression and drug sensitivity"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0265-6970","authenticated-orcid":false,"given":"Ying Z.","family":"Mazzu","sequence":"first","affiliation":[{"name":"Department of Medicine Memorial Sloan Kettering Cancer Center  New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"YuRou","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Medicine Memorial Sloan Kettering Cancer Center  New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Subhiksha","family":"Nandakumar","sequence":"additional","affiliation":[{"name":"Center for Molecular Oncology Memorial Sloan Kettering Cancer Center  New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Sj\u00f6str\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology University of California San Francisco  CA USA"},{"name":"Division of Hematology and Oncology Department of Medicine University of California San Francisco  CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lina E.","family":"Jehane","sequence":"additional","affiliation":[{"name":"Department of Medicine Memorial Sloan Kettering Cancer Center  New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Romina","family":"Ghale","sequence":"additional","affiliation":[{"name":"Department of Medicine Memorial Sloan Kettering Cancer Center  New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barani","family":"Govindarajan","sequence":"additional","affiliation":[{"name":"Department of Pathology Wayne State University  Detroit MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Travis A.","family":"Gerke","sequence":"additional","affiliation":[{"name":"Prostate Cancer Clinical Trials Consortium  New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gwo\u2010Shu Mary","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medicine Dana\u2010Farber Cancer Institute  Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian\u2010Hua","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Pittsburgh School of Medicine  PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sreenivasa R.","family":"Chinni","sequence":"additional","affiliation":[{"name":"Department of Pathology Wayne State University  Detroit MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorelei A.","family":"Mucci","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Harvard T.H. Chan School of Public Health  Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felix Y.","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology University of California San Francisco  CA USA"},{"name":"Division of Hematology and Oncology Department of Medicine University of California San Francisco  CA USA"},{"name":"Helen Diller Family Comprehensive Cancer Center University of California San Francisco  CA USA"},{"name":"Department of Urology University of California San Francisco  CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip W.","family":"Kantoff","sequence":"additional","affiliation":[{"name":"Department of Medicine Memorial Sloan Kettering Cancer Center  New York NY 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