{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:11:06Z","timestamp":1792069866780,"version":"4.4.0"},"reference-count":54,"publisher":"Cold Spring Harbor Laboratory","issue":"17","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Dev."],"published-print":{"date-parts":[[2003,9,1]]},"abstract":"<jats:p>\n                    Desmoplastic small round cell tumor (DSRCT) is defined by a chimeric transcription factor, resulting from fusion of the N-terminal domain of the Ewing's sarcoma gene\n                    <jats:italic>EWS<\/jats:italic>\n                    to the three C-terminal zinc fingers of the Wilms' tumor suppressor\n                    <jats:italic>WT1<\/jats:italic>\n                    . Although DNA-binding sites have been defined for the uninterrupted\n                    <jats:italic>WT1<\/jats:italic>\n                    zinc finger domains, the most prevalent isoforms of both WT1 and EWS\u2013WT1 have an insertion of three amino acids [lysine, threonine, and serine (KTS)], which abrogates binding to known consensus sequences and transactivation of known target genes. Here, we used cDNA subtractive hybridization to identify an endogenous gene,\n                    <jats:italic>LRRC15<\/jats:italic>\n                    , which is specifically up-regulated after inducible expression of\n                    <jats:italic>EWS\u2013WT1(+KTS)<\/jats:italic>\n                    in cancer cell lines, and is expressed within primary DSRCT cells. The chimeric protein binds in vitro and in vivo to a specific element upstream of\n                    <jats:italic>LRRC15<\/jats:italic>\n                    , leading to dramatic transcriptional activation. Mutagenesis studies define the optimal binding site of the (+KTS) isoform of EWS\u2013WT1 as 5\u2032-GGAGG(A\/G)-3\u2032.\n                    <jats:italic>LRRC15<\/jats:italic>\n                    encodes a leucine-rich transmembrane protein, present at the leading edge of migrating cells, the expression of which in normal tissues is restricted to the invasive cytotrophoblast layer of the placenta; small interfering (siRNA)-mediated suppression of\n                    <jats:italic>LRRC15<\/jats:italic>\n                    expression in breast cancer cells leads to abrogation of invasiveness in vitro. Together, these observations define the consequence of (KTS) insertion within WT1-derived zinc fingers, and identify a novel EWS\u2013WT1 transcriptional target implicated in tumor invasiveness.\n                  <\/jats:p>","DOI":"10.1101\/gad.1110703","type":"journal-article","created":{"date-parts":[[2003,8,18]],"date-time":"2003-08-18T20:46:13Z","timestamp":1061239573000},"page":"2094-2107","source":"Crossref","is-referenced-by-count":51,"title":["Identification of a DNA-binding site and transcriptional target for the EWS\u2013WT1(+KTS) oncoprotein"],"prefix":"10.1101","volume":"17","author":[{"given":"Paul A.","family":"Reynolds","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gromoslaw A.","family":"Smolen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel E.","family":"Palmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Sgroi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay","family":"Yajnik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William L.","family":"Gerald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A.","family":"Haber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[2003,1,1]]},"reference":[{"key":"2021111519023407000_17.17.2094.1","first-page":"3239","volume":"47","year":"1987","journal-title":"Cancer Res."},{"key":"2021111519023407000_17.17.2094.2","doi-asserted-by":"publisher","DOI":"10.1007\/s004280050147"},{"key":"2021111519023407000_17.17.2094.3","doi-asserted-by":"publisher","DOI":"10.1038\/ng1297-467"},{"key":"2021111519023407000_17.17.2094.4","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1128\/MCB.18.3.1489","volume":"18","year":"1998","journal-title":"Mol. 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