{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T19:12:45Z","timestamp":1784661165033,"version":"3.55.0"},"reference-count":21,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,10,31]],"date-time":"2013-10-31T00:00:00Z","timestamp":1383177600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J Experimental Path"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>A recent global gene expression profiling study unexpectedly showed that activated oncogenic <jats:styled-content style=\"fixed-case\">NRAS<\/jats:styled-content> may recruit neural precursor cell expressed, developmentally downregulated 4<jats:styled-content style=\"fixed-case\">L<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>edd4<jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>; a human homologue of <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>edd4\u20102) in cultured melanoma cells. However, whether <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>edd4<jats:styled-content style=\"fixed-case\">L<\/jats:styled-content> was expressed in melanoma tissues or participated in melanoma carcinogenesis remains to be clarified. Here, we investigated the expression status of <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>edd4<jats:styled-content style=\"fixed-case\">L<\/jats:styled-content> in human melanocytes, benign nevi and melanoma tissue specimens and subsequently attempted to determine the role of <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>edd4<jats:styled-content style=\"fixed-case\">L<\/jats:styled-content> in melanoma cell growth. Immunohistochemical staining revealed that <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>edd4<jats:styled-content style=\"fixed-case\">L<\/jats:styled-content> was not present in any non\u2010tumorous melanocytes or in 18 benign nevi tissues, but it was detected in 34 of 79 cutaneous melanomas and 9 of 32 nodal metastatic melanomas. Downregulation of <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>edd4<jats:styled-content style=\"fixed-case\">L<\/jats:styled-content> significantly reduced the growth of cultured <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>361 melanoma cells <jats:italic>in vitro<\/jats:italic>. Moreover, exogenous <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>edd4<jats:styled-content style=\"fixed-case\">L<\/jats:styled-content> expression significantly promoted the growth of <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>2058 melanoma cells <jats:italic>in vivo<\/jats:italic> in a xenograft assay. The present findings indicate that <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>edd4<jats:styled-content style=\"fixed-case\">L<\/jats:styled-content> expression may be increased to facilitate tumour growth in many melanomas.<\/jats:p>","DOI":"10.1111\/iep.12051","type":"journal-article","created":{"date-parts":[[2013,10,31]],"date-time":"2013-10-31T11:03:59Z","timestamp":1383217439000},"page":"24-28","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Pathobiological properties of the ubiquitin ligase <scp>N<\/scp>edd4<scp>L<\/scp> in melanoma"],"prefix":"10.1111","volume":"95","author":[{"given":"Yusuke","family":"Kito","sequence":"first","affiliation":[{"name":"Department of Immunopathology Gifu University Graduate School of Medicine Gifu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juncheng","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Immunopathology Gifu University Graduate School of Medicine Gifu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoe","family":"Goto","sequence":"additional","affiliation":[{"name":"Department of Immunopathology Gifu University Graduate School of Medicine Gifu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Okubo","sequence":"additional","affiliation":[{"name":"Department of Immunopathology Gifu University Graduate School of Medicine Gifu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Adachi","sequence":"additional","affiliation":[{"name":"Department of Pathology Kochi Medical School Nankoku Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Nagayama","sequence":"additional","affiliation":[{"name":"Innovation Satellite Kochi Practical Application Research Japan Science and Technology Agency Kami Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamotsu","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Department of Immunopathology Gifu University Graduate School of Medicine Gifu Japan"},{"name":"Department of Pathology Kochi Medical School Nankoku Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,10,31]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2405044"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1103782"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1586\/era.10.170"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.20873"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.23876"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1002011"},{"key":"e_1_2_7_8_1","doi-asserted-by":"crossref","first-page":"858425","DOI":"10.1155\/2011\/858425","article-title":"Worldwide increasing incidences of cutaneous malignant melanoma","volume":"2011","author":"Godar D.E.","year":"2011","journal-title":"J. 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