{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:46:22Z","timestamp":1787013982567,"version":"build-2736575974"},"reference-count":42,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24K10355"],"award-info":[{"award-number":["24K10355"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K24026"],"award-info":[{"award-number":["23K24026"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Melanoma heterogeneity contributes to increased metastatic potential. Although a subpopulation characterized by MITF\n                    <jats:sup>low<\/jats:sup>\n                    \/AXL\n                    <jats:sup>high<\/jats:sup>\n                    has been linked to invasiveness, the underlying mechanisms remain unclear. In this study, we identified cell migration\u2010related gene sets as significantly enriched after the knockdown of SOX10 in melanoma. Both\n                    <jats:italic>in silico<\/jats:italic>\n                    analysis and in vitro analysis identified ITGA3 and EPHA2 as downstream effectors of SOX10\u2010mediated migration, essential for cell adhesion and random motility, respectively. Moreover, the oncogenic activation of MAPK was necessary for increased random motility through EphA2 phosphorylation at the Ser 897 residue. We also identified IRF1 as an upstream regulator of both ITGA3 and EphA2 after the knockdown of SOX10. Notably, IRF1 suppression or the treatment with the FAK inhibitor, defactinib, significantly reduced melanoma metastasis in vivo. These findings demonstrate that the reduced expression of SOX10 promotes melanoma metastasis through the IRF1\u2010ITGA3\/EphA2\u2010FAK pathway and highlight FAK inhibition as a potential therapeutic strategy.\n                  <\/jats:p>","DOI":"10.1111\/cas.70173","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T05:36:39Z","timestamp":1755149799000},"page":"3052-3065","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>SOX10<\/scp>\n                    Regulates Melanoma Metastasis Through the\n                    <scp>IRF1<\/scp>\n                    \u2010\n                    <scp>ITGA3<\/scp>\n                    \/\n                    <scp>EphA2<\/scp>\n                    \u2010\n                    <scp>FAK<\/scp>\n                    Pathway"],"prefix":"10.1111","volume":"116","author":[{"given":"Ryuya","family":"Kaminaka","sequence":"first","affiliation":[{"name":"Department of Cancer Cell Biology, Faculty of Pharmaceutical Sciences University of Toyama  Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nana","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Cancer Cell Biology, Faculty of Pharmaceutical Sciences University of Toyama  Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayu","family":"Nishizawa","sequence":"additional","affiliation":[{"name":"Department of Cancer Cell Biology, Faculty of Pharmaceutical Sciences University of Toyama  Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9092-7181","authenticated-orcid":false,"given":"Soichiro","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Division of Pathogenic Biochemistry, Institute of 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