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This study aimed to explore the mechanism of SCLC metastasis using an originally developed orthotopic transplantation model with DMS273 cells. An analysis of G3H cells, a highly metastatic subline of DMS273 cells, revealed that claudin\u201011 promotes the invasive and metastatic ability of the cells. Further analysis revealed that membrane type 1\u2010matrix metalloproteinase (MT1\u2010MMP), which degrades a wide range of extracellular matrix components, was coprecipitated with claudin\u201011. Gelatin zymography revealed that claudin\u201011 enhanced MT1\u2010MMP activity, and <jats:italic>MT1\u2010MMP<\/jats:italic> silencing suppressed the invasive and metastatic ability of G3H cells. Moreover, in <jats:italic>MT1\u2010MMP<\/jats:italic> silencing DMS273 cells, the enhancement of invasion and metastatic potential induced by <jats:italic>CLDN11<\/jats:italic> overexpression was abolished. These results demonstrate that claudin\u201011 enhances the invasive capacity of the cells by activating MT1\u2010MMP, which promotes metastatic formation in the orthotopic transplantation model. Additionally, claudin\u201011 expression was detected in SCLC tumor samples, and higher expression of <jats:italic>CLDN11<\/jats:italic> correlated with poor prognosis in patients with SCLC. These findings suggest that the claudin\u201011\/MT1\u2010MMP axis plays an important role in SCLC pathogenesis.<\/jats:p>","DOI":"10.1111\/cas.70038","type":"journal-article","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T12:19:02Z","timestamp":1741868342000},"page":"1773-1784","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Claudin\u201011 Enhances Invasive and Metastatic Abilities of Small\u2010Cell Lung Cancer Through <scp>MT1<\/scp>\u2010<scp>MMP<\/scp> Activation"],"prefix":"10.1111","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9396-9475","authenticated-orcid":false,"given":"Shuichi","family":"Sakamoto","sequence":"first","affiliation":[{"name":"Institute of Microbial Chemistry (BIKAKEN), Numazu Microbial Chemistry Research Foundation  Numazu 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