{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T15:04:44Z","timestamp":1788966284864,"version":"build-2803163510"},"reference-count":75,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2023,12,14]],"date-time":"2023-12-14T00:00:00Z","timestamp":1702512000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Emerging evidence shows that oral squamous cell carcinoma (OSCC) invasiveness can be attributed to a small subpopulation of cancer stem cells (CSCs) in the bulk of the tumor. However, the presence of CSCs in the OSCC close resection margins is still poorly unexplored. Here, we found that <jats:italic>BMI1<\/jats:italic>, <jats:italic>CD44<\/jats:italic>, <jats:italic>SOX2<\/jats:italic>, <jats:italic>OCT4<\/jats:italic>, <jats:italic>UBE2C<\/jats:italic>, <jats:italic>CXCR4<\/jats:italic> CSCs marker genes are significantly upregulated, while <jats:italic>IGF1-R<\/jats:italic>, <jats:italic>KLF4<\/jats:italic>, <jats:italic>ALDH1A1<\/jats:italic>, <jats:italic>CD133<\/jats:italic>, <jats:italic>FAM3C<\/jats:italic> are downregulated in the tumor core <jats:italic>vs<\/jats:italic> healthy mucosa of 24 patients with OSCC. Among these, <jats:italic>SOX2<\/jats:italic> appears also upregulated in the tumor close margin <jats:italic>vs<\/jats:italic> healthy mucosa and this significantly correlates with tumor size and lymph node compromise. <jats:italic>In vitro<\/jats:italic> analyses in CAL27 and SCC15 tongue squamous cell carcinoma cell lines, show that <jats:italic>SOX2<\/jats:italic> transient knockdown i) promotes the mesenchymal-to-epithelial transition, ii) smooths the invasiveness, iii) attenuates the 3D tumor sphere-forming capacity, and iv) partially increases the sensitivity to cisplatin treatment. Overall, our study highlights that the OSCC close margins can retain CSC-specific markers. Notably, <jats:italic>SOX2<\/jats:italic> may represent a useful CSCs marker to predict a more aggressive phenotype and a suitable target to prevent local invasiveness.<\/jats:p>","DOI":"10.1371\/journal.pone.0293475","type":"journal-article","created":{"date-parts":[[2023,12,14]],"date-time":"2023-12-14T18:28:54Z","timestamp":1702578534000},"page":"e0293475","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["SOX2 promotes a cancer stem cell-like phenotype and local spreading in oral squamous cell carcinoma"],"prefix":"10.1371","volume":"18","author":[{"given":"Alessandro","family":"Sacco","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna 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