{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T14:49:05Z","timestamp":1788446945430,"version":"build-2803163510"},"reference-count":53,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T00:00:00Z","timestamp":1684713600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["101\u20102314\u2010B\u2010002\u2010174, 102\u20102314\u2010B\u2010002\u2010098, and 103\u201023"],"award-info":[{"award-number":["101\u20102314\u2010B\u2010002\u2010174, 102\u20102314\u2010B\u2010002\u2010098, and 103\u201023"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>In lung cancer patients, most deaths are caused by the distant dissemination of cancer cells. Epithelial\u2013mesenchymal transition (EMT) and collective cell migration are distinct and important mechanisms involved in cancer invasion and metastasis. Additionally, microRNA dysregulation contributes significantly to cancer progression. In this study, we aimed to explore the function of miR\u2010503 in cancer metastasis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Molecular manipulations (silencing or overexpression) were performed to investigate the biological functions of miR\u2010503 including migration and invasion. Reorganization of cytoskeleton was assessed using immunofluorescence and the relationship between miR\u2010503 and downstream protein tyrosine kinase 7 (PTK7) was assessed using quantitative real\u2010time PCR, immunoblotting, and reporter assays. The tail vein metastatic animal experiments were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Herein, we demonstrated that the downregulation of miR\u2010503 confers an invasive phenotype in lung cancer cells and provided in vivo evidence that miR\u2010503 significantly inhibits metastasis. We found that miR\u2010503 inversely regulates EMT, identified PTK7 as a novel miR\u2010503 target, and showed the functional effects of miR\u2010503 on cell migration and invasion were restored upon reconstitution of PTK7 expression. As PTK7 is a Wnt\/planar cell polarity protein crucial for collective cell movement, these results implicated miR\u2010503 in both EMT and collective migration. However, the expression of PTK7 did not influence EMT induction, suggesting that miR\u2010503 regulates EMT through mechanisms other than PTK7 inhibition. Furthermore, we discovered that PTK7 mechanistically activates focal adhesion kinase (FAK) and paxillin, thereby controlling the reorganization of the cortical actin cytoskeleton.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Collectively, miR\u2010503 is capable of governing EMT and PTK7\/FAK signaling independently to control the invasion and dissemination of lung cancer cells, indicating that miR\u2010503 represents a pleiotropic regulator of cancer metastasis and hence a potential therapeutic target for lung cancer.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.6116","type":"journal-article","created":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T12:09:10Z","timestamp":1684757350000},"page":"14511-14525","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["MiR\u2010503 pleiotropically regulates epithelial\u2010mesenchymal transition and targets PTK7 to control lung cancer metastasis"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7532-2264","authenticated-orcid":false,"given":"Tzu\u2010Hsiu","family":"Tsai","sequence":"first","affiliation":[{"name":"Department of Internal Medicine National Taiwan University Hospital  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6104-3459","authenticated-orcid":false,"given":"Chien\u2010Hung","family":"Gow","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Far Eastern Memorial Hospital  New Taipei City Taiwan"},{"name":"Department of Healthcare Information and Management Ming\u2010Chuan University  Taoyuan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Nan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine National Taiwan University Hospital  Taipei 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