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Multiple subunits of the chromatin remodeling BAF complex, including ARID1A, play a role in oncogenesis, either as tumor suppressors or oncogenes. Recent work demonstrated that EWS\u2013FLI1, the oncogenic driver of Ewing sarcoma (ES), plays a role in chromatin regulation through interactions with the BAF complex. However, the specific BAF subunits that interact with EWS\u2013FLI1 and the precise role of the BAF complex in ES oncogenesis remain unknown. In addition to regulating transcription, EWS\u2013FLI1 also alters the splicing of many mRNA isoforms, but the role of splicing modulation in ES oncogenesis is not well understood. We have identified a direct connection between the EWS\u2013FLI1 protein and ARID1A isoform protein variant ARID1A-L. We demonstrate here that ARID1A-L is critical for ES maintenance and supports oncogenic transformation. We further report a novel feed-forward cycle in which EWS\u2013FLI1 leads to preferential splicing of ARID1A-L, promoting ES growth, and ARID1A-L reciprocally promotes EWS\u2013FLI1 protein stability. Dissecting this interaction may lead to improved cancer-specific drug targeting.<\/jats:p>","DOI":"10.1093\/nar\/gkz699","type":"journal-article","created":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T19:11:44Z","timestamp":1564686704000},"source":"Crossref","is-referenced-by-count":13,"title":["EWS\u2013FLI1 modulated alternative splicing of ARID1A reveals novel oncogenic function through the BAF complex"],"prefix":"10.1093","author":[{"given":"Saravana\u00a0P","family":"Selvanathan","sequence":"first","affiliation":[{"name":"Departments of Oncology and Pediatrics, Georgetown University, Washington, DC 20057, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1097-0962","authenticated-orcid":false,"given":"Garrett\u00a0T","family":"Graham","sequence":"additional","affiliation":[{"name":"Departments of Oncology and Pediatrics, Georgetown University, Washington, DC 20057, USA"}]},{"given":"Alexander\u00a0R","family":"Grego","sequence":"additional","affiliation":[{"name":"Departments of Oncology and Pediatrics, Georgetown University, Washington, DC 20057, USA"}]},{"given":"Tabari\u00a0M","family":"Baker","sequence":"additional","affiliation":[{"name":"Caris Life Sciences, Phoenix, AZ, USA"}]},{"given":"J\u00a0Robert","family":"Hogg","sequence":"additional","affiliation":[{"name":"Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD,\u00a0USA"}]},{"given":"Mark","family":"Simpson","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers University, Newark, NJ 07103, USA"}]},{"given":"Mona","family":"Batish","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers University, Newark, NJ 07103, USA"},{"name":"Department of Medical and Molecular Sciences, University of Delaware, Newark, DE 19716, USA"}]},{"given":"Brian","family":"Crompton","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA, USA"},{"name":"Broad Institute, Cambridge, MA, USA"}]},{"given":"Kimberly","family":"Stegmaier","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA, USA"},{"name":"Broad Institute, Cambridge, MA, USA"}]},{"given":"Eleni\u00a0M","family":"Tomazou","sequence":"additional","affiliation":[{"name":"Children's Cancer Research Institute, St. Anna Kinderkrebsforschung, Vienna, Austria"}]},{"given":"Heinrich","family":"Kovar","sequence":"additional","affiliation":[{"name":"Children's Cancer Research Institute, St. Anna Kinderkrebsforschung, Vienna, Austria"},{"name":"Department of Pediatrics, Medical University of Vienna, Vienna, Austria"}]},{"given":"Aykut","family":"\u00dcren","sequence":"additional","affiliation":[{"name":"Departments of Oncology and Pediatrics, Georgetown University, Washington, DC 20057, USA"}]},{"given":"Jeffrey\u00a0A","family":"Toretsky","sequence":"additional","affiliation":[{"name":"Departments of Oncology and Pediatrics, Georgetown University, Washington, DC 20057, USA"}]}],"member":"286","published-online":{"date-parts":[[2019,8,8]]},"reference":[{"key":"2019080805045217000_B1","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1016\/j.celrep.2015.10.046","article-title":"Loss of BAF (mSWI\/SNF) complexes causes global transcriptional and chromatin state changes in forebrain development","volume":"13","author":"Narayanan","year":"2015","journal-title":"Cell Rep."},{"key":"2019080805045217000_B2","doi-asserted-by":"crossref","first-page":"a026930","DOI":"10.1101\/cshperspect.a026930","article-title":"The many roles of BAF (mSWI\/SNF) and PBAF complexes in cancer","volume":"6","author":"Hodges","year":"2016","journal-title":"Cold Spring Harbor Perspect. 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