{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:50:36Z","timestamp":1787313036932,"version":"build-2736575974"},"reference-count":35,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,8,21]],"date-time":"2024-08-21T00:00:00Z","timestamp":1724198400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Thymic epithelial tumors (TETs) are rare tumors arising from the mediastinum. Among TETs, thymoma type B2, B3 and thymic carcinoma are highly malignant and often present invasion and dissemination. However, the biological characteristics of TETs have not been thoroughly studied, and their mechanisms of invasion and dissemination are largely unknown. \u03b1\u2010Actinin 4 (ACTN4) is a member of actin\u2010binding proteins and reportedly plays important roles in the progression of several cancers. In this study, we investigated the relationship between ACTN4 and characteristics of the malignant potential of TETs, such as invasion and dissemination.\n                    <jats:italic>In vitro<\/jats:italic>\n                    experiments using Ty\u201082 thymic carcinoma cells revealed that overexpression of ACTN4 enhanced the proliferative and invasive ability of Ty\u201082 cells; conversely, knockdown of ACTN4 attenuated the proliferative and invasive potential of Ty\u201082 cells. In western blotting (WB) experiments, ACTN4 induced the phosphorylation of extracellular signal\u2013regulated kinase and glycogen synthase kinase 3\u03b2 to regulate the \u03b2\u2010catenin\/Slug pathway. Furthermore, WB analysis of cancer tissue\u2013origin spheroids from patients with TETs showed results similar to those for Ty\u201082 cells. In\u00a0vivo experiments showed that the knockdown of ACTN4 significantly suppressed the dissemination of Ty\u201082 cells. A WB and immunohistochemistry staining comparison of primary and disseminated lesions of TETs using surgical specimens showed upregulated expression of ACTN4, \u03b2\u2010catenin, and Slug proteins in disseminated lesions. In summary, our study suggests ACTN4 is associated with malignant potential characteristics such as invasion and dissemination in TETs via the \u03b2\u2010catenin\/Slug pathway.\n                  <\/jats:p>","DOI":"10.1111\/cas.16313","type":"journal-article","created":{"date-parts":[[2024,8,21]],"date-time":"2024-08-21T22:28:14Z","timestamp":1724279294000},"page":"3636-3647","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>ACTN4<\/scp>\n                    is associated with the malignant potential of thymic epithelial tumors through the \u03b2\u2010catenin\/Slug pathway"],"prefix":"10.1111","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9928-7245","authenticated-orcid":false,"given":"Hideki","family":"Nagata","sequence":"first","affiliation":[{"name":"Department of General Thoracic Surgery, Graduate School of Medicine Osaka University  Suita 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