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The POU domain transcription factor BRN2 is a key regulator of melanoma invasion, yet its role in melanoma initiation remains unknown. Here, in a\n                    <jats:italic>Braf<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>V600E<\/jats:italic>\n                    <\/jats:sup>\n                    <jats:italic>Pten<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>F\/+<\/jats:italic>\n                    <\/jats:sup>\n                    context, we show that\n                    <jats:italic>BRN2<\/jats:italic>\n                    haplo-insufficiency promotes melanoma initiation and metastasis. However, metastatic colonization is less efficient in the absence of Brn2. Mechanistically, BRN2 directly induces\n                    <jats:italic>PTEN<\/jats:italic>\n                    expression and in consequence represses PI3K signaling. Moreover, MITF, a BRN2 target, represses\n                    <jats:italic>PTEN<\/jats:italic>\n                    transcription. Collectively, our results suggest that on a\n                    <jats:italic>PTEN<\/jats:italic>\n                    heterozygous background somatic deletion of one\n                    <jats:italic>BRN2<\/jats:italic>\n                    allele and temporal regulation of the other allele elicits melanoma initiation and progression.\n                  <\/jats:p>","DOI":"10.1038\/s41467-021-23973-5","type":"journal-article","created":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T06:03:09Z","timestamp":1623909789000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["BRN2 is a non-canonical melanoma tumor-suppressor"],"prefix":"10.1038","volume":"12","author":[{"given":"Michael","family":"Hamm","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2341-6848","authenticated-orcid":false,"given":"Pierre","family":"Sohier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Petit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00e9my H.","family":"Raymond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7368-3664","authenticated-orcid":false,"given":"V\u00e9ronique","family":"Delmas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine","family":"Le Coz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franck","family":"Gesbert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"Kenny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zackie","family":"Aktary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Pouteaux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Rambow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Sarasin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nisamanee","family":"Charoenchon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Bellacosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9537-7761","authenticated-orcid":false,"given":"Luis","family":"Sanchez-del-Campo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Mosteo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Lauss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8461-6341","authenticated-orcid":false,"given":"Dies","family":"Meijer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eirikur","family":"Steingrimsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00f6ran B.","family":"J\u00f6nsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Cornell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5533-1171","authenticated-orcid":false,"given":"Irwin","family":"Davidson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1614-3909","authenticated-orcid":false,"given":"Colin R.","family":"Goding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2010-6107","authenticated-orcid":false,"given":"Lionel","family":"Larue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,17]]},"reference":[{"key":"23973_CR1","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1038\/nature00766","volume":"417","author":"H Davies","year":"2002","unstructured":"Davies, H. et al. 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