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We have identified the receptor protein tyrosine kinase TYRO3 as an upstream regulator of\n                    <jats:italic>MITF<\/jats:italic>\n                    expression by a genome-wide gain-of-function cDNA screen and show that TYRO3 induces\n                    <jats:italic>MITF-M<\/jats:italic>\n                    expression in a SOX10-dependent manner in melanoma cells. Expression of\n                    <jats:italic>TYRO3<\/jats:italic>\n                    is significantly elevated in human primary melanoma tissue samples and melanoma cell lines and correlates with\n                    <jats:italic>MITF-M<\/jats:italic>\n                    mRNA levels.\n                    <jats:italic>TYRO3<\/jats:italic>\n                    overexpression bypasses BRAF(V600E)-induced senescence in primary melanocytes, inducing transformation of non-tumorigenic cell lines. Furthermore, TYRO3 knockdown represses cellular proliferation and colony formation in melanoma cells, and sensitizes them to chemotherapeutic agent-induced apoptosis;\n                    <jats:italic>TYRO3<\/jats:italic>\n                    knockdown in melanoma cells also inhibits tumorigenesis in vivo. Taken together, these data indicate that TYRO3 may serve as a target for the development of therapeutic agents for melanoma.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0909292106","type":"journal-article","created":{"date-parts":[[2009,9,23]],"date-time":"2009-09-23T22:40:49Z","timestamp":1253745649000},"page":"17025-17030","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":87,"title":["A genomic screen identifies TYRO3 as a MITF regulator in melanoma"],"prefix":"10.1073","volume":"106","author":[{"given":"Shoutian","family":"Zhu","sequence":"first","affiliation":[{"name":"The Skaggs Institute of Chemical Biology and the Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiko","family":"Wurdak","sequence":"additional","affiliation":[{"name":"The Skaggs Institute of Chemical Biology and the Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Galkin","sequence":"additional","affiliation":[{"name":"Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Tao","sequence":"additional","affiliation":[{"name":"Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[{"name":"Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Costas A.","family":"Lyssiotis","sequence":"additional","affiliation":[{"name":"The Skaggs Institute of Chemical Biology and the Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Yan","sequence":"additional","affiliation":[{"name":"Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Buu P.","family":"Tu","sequence":"additional","affiliation":[{"name":"Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loren","family":"Miraglia","sequence":"additional","affiliation":[{"name":"Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Walker","sequence":"additional","affiliation":[{"name":"Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanxiang","family":"Sun","sequence":"additional","affiliation":[{"name":"Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Orth","sequence":"additional","affiliation":[{"name":"Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter G.","family":"Schultz","sequence":"additional","affiliation":[{"name":"The Skaggs Institute of Chemical Biology and the Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037; and"},{"name":"Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Wu","sequence":"additional","affiliation":[{"name":"Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,10,6]]},"reference":[{"key":"e_1_3_3_1_2","article-title":"Solar ultraviolet radiation: Global burden of disease from solar ultraviolet radiation","author":"Lucas R","year":"2006","unstructured":"R Lucas, T McMichael, W Smith, B Armstrong, Solar ultraviolet radiation: Global burden of disease from solar ultraviolet radiation. 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