{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T07:22:44Z","timestamp":1769066564976,"version":"3.49.0"},"reference-count":59,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2017,7,11]],"date-time":"2017-07-11T00:00:00Z","timestamp":1499731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16K08579"],"award-info":[{"award-number":["16K08579"]}],"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":["15H06234"],"award-info":[{"award-number":["15H06234"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:p>Cutaneous melanoma is the most aggressive form of skin cancer. This aggressiveness appears to be due to the cancer cells' ability to reversibly switch between phenotypes with non\u2010invasive and invasive potential, and microphthalmia\u2010associated transcription factor (<jats:styled-content style=\"fixed-case\">MITF<\/jats:styled-content>) is known to play a central role in this process. The transcription factor glioma\u2010associated oncogene homolog 1 (<jats:styled-content style=\"fixed-case\">GLI<\/jats:styled-content>1) is a component of the canonical and noncanonical sonic hedgehog pathways. Although <jats:styled-content style=\"fixed-case\">GLI<\/jats:styled-content>1 has been suggested to be involved in melanoma progression, its precise role and the mechanism underlying invasion remain unclear. Here we investigated whether and how <jats:styled-content style=\"fixed-case\">GLI<\/jats:styled-content>1 is involved in the invasive ability of melanoma cells. <jats:italic>Gli1<\/jats:italic> knockdown (<jats:styled-content style=\"fixed-case\">KD<\/jats:styled-content>) melanoma cell lines, established by using <jats:italic>Gli1<\/jats:italic>\u2010targeting lentiviral short hairpin <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>, exhibited a markedly reduced invasion ability, but their <jats:styled-content style=\"fixed-case\">MITF<\/jats:styled-content> expression and activity were the same as controls. <jats:italic>Gli1 <\/jats:italic><jats:styled-content style=\"fixed-case\">KD<\/jats:styled-content> melanoma cells also led to less lung metastasis in mice compared with control melanoma cells. Furthermore, the <jats:italic>Gli1 <\/jats:italic><jats:styled-content style=\"fixed-case\">KD<\/jats:styled-content> melanoma cells underwent a mesenchymal\u2010to\u2010epithelial\u2010like transition, accompanied by downregulation of the epithelial\u2010to\u2010mesenchymal transition (<jats:styled-content style=\"fixed-case\">EMT<\/jats:styled-content>)\u2010inducing transcription factors (<jats:styled-content style=\"fixed-case\">EMT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">TF<\/jats:styled-content>) <jats:italic>Snail1<\/jats:italic>,<jats:italic> Zeb1<\/jats:italic> and <jats:italic>Twist1<\/jats:italic>, but not <jats:italic>Snail2<\/jats:italic> or <jats:italic>Zeb2<\/jats:italic>. Collectively, these results indicate that <jats:styled-content style=\"fixed-case\">GLI<\/jats:styled-content>1 is important for maintaining the invasive and mesenchymal\u2010like properties of melanoma cells independent of <jats:styled-content style=\"fixed-case\">MITF<\/jats:styled-content>, most likely by modulating a subset of <jats:styled-content style=\"fixed-case\">EMT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">TF<\/jats:styled-content>. Our findings provide new insight into how heterogeneity and plasticity are achieved and regulated in melanoma.<\/jats:p>","DOI":"10.1111\/cas.13294","type":"journal-article","created":{"date-parts":[[2017,6,21]],"date-time":"2017-06-21T08:22:39Z","timestamp":1498033359000},"page":"1602-1611","source":"Crossref","is-referenced-by-count":15,"title":["Critical role of glioma\u2010associated oncogene homolog 1 in maintaining invasive and mesenchymal\u2010like properties of melanoma cells"],"prefix":"10.1111","volume":"108","author":[{"given":"I Ketut","family":"Gunarta","sequence":"first","affiliation":[{"name":"Division of Molecular Cell Signaling Cancer Research Institute Kanazawa University Kanazawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Molecular Cell Signaling Cancer Research Institute Kanazawa University Kanazawa 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