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Recent studies have reported that <jats:italic>SPOCK2<\/jats:italic> plays important roles in the progression of various human cancers; however, the role of <jats:italic>SPOCK2<\/jats:italic> in melanoma remains unknown. Therefore, this study investigated the roles of <jats:italic>SPOCK2<\/jats:italic> and the related mechanisms in melanoma progression. To evaluate the clinical significance of <jats:italic>SPOCK2<\/jats:italic> expression in patients with melanoma, we analysed the association between <jats:italic>SPOCK2<\/jats:italic> expression and its prognostic value for patients with melanoma using systematic multiomic analysis. Subsequently, to investigate the roles of <jats:italic>Spock2<\/jats:italic> in melanoma progression in\u00a0vitro and in\u00a0vivo, we knocked down <jats:italic>Spock2<\/jats:italic> in the B16F10 melanoma cell line. High <jats:italic>SPOCK2<\/jats:italic> levels were positively associated with good prognosis and long survival rate of patients with melanoma. <jats:italic>Spock2<\/jats:italic> knockdown promoted melanoma cell proliferation by inducing the cell cycle and inhibiting apoptosis. Moreover, <jats:italic>Spock2<\/jats:italic> downregulation significantly increased cell migration and invasion by upregulating MMP2 and MT1\u2010MMP. The increased cell proliferation and migration were inhibited by MAPK inhibitor, and ERK phosphorylation was considerably enhanced in <jats:italic>Spock2<\/jats:italic> knockdown cells. Therefore, <jats:italic>Spock2<\/jats:italic> could function as a tumour suppressor gene to regulate melanoma progression by regulating the MAPK\/ERK signalling pathway. Additionally, <jats:italic>Spock2<\/jats:italic> knockdown cell injection induced considerable tumour growth and lung metastasis in C57BL6 mice compared to that in the control group. Our findings suggest that <jats:italic>SPOCK2<\/jats:italic> plays crucial roles in malignant progression of melanoma and functions as a novel therapeutic target of melanoma.<\/jats:p>","DOI":"10.1111\/exd.15092","type":"journal-article","created":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T11:28:05Z","timestamp":1718710085000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The novel prognostic marker <scp>SPOCK2<\/scp> regulates tumour progression in melanoma"],"prefix":"10.1111","volume":"33","author":[{"given":"Ji Young","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Health Industry Sookmyung Women's University  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyeijin","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Health Industry Sookmyung Women's University  Seoul 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