{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T22:04:50Z","timestamp":1784153090504,"version":"3.55.0"},"reference-count":36,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The development of\u00a0resistance to anticancer therapies in cancer cell is a major challenge in the treatment of oral squamous cell carcinoma (OSCC), a common malignant tumor. Erythropoietin\u2010producing hepatocellular A2 (EphA2) affects several cancers, and this study examined its role in enhancing OSCC. Following screening, EphA2 and SRY\u2010Box transcription factor 8 (SOX8) knocked down and overexpression cell lines were constructed, followed by treatment with Cetuximab. Quantitative real\u2010time polymerase chain reaction, western blot, cell counting kit\u20108, wound healing, and transwell assay\u00a0were used to detect the relevant indicators. Co\u2010immunoprecipitation was used to detect the interaction between EphA2 and SH2 domain\u2010containing protein\u2010tyrosine phosphatase\u20102 (SHP2). Double luciferase reporter gene experiment and chromatin immunoprecipitation experiment were performed to verify the regulatory mechanism of EphA2 and SOX8. The mouse tumor model was established, and the tumor development was observed after plasmid transfection and Cetuximab treatment. EphA2 was highly expressed in OSCC cells, and overexpression of EphA2 up\u2010regulated SOX8. EphA2 regulated SOX8 and associated protein expression to increase OSCC cell migration and invasion. EphA2 knockdown made OSCC cells more sensitive to Cetuximab, whereas SOX8 overexpression reduced this sensitivity. We found SHP2 bound to SOX8. Down\u2010regulation of EphA2 decreased tumor growth in mice, increased Cetuximab sensitivity, and overexpression of SOX8\/SHP2 decreased Cetuximab sensitivity. OSCC had elevated EphA2 levels, which enhanced cell migration and invasion via SHP2\/SOX8 and impaired Cetuximab sensitivity. Down\u2010regulation of EphA2 decreased tumor growth and enhanced Cetuximab sensitivity, suggesting new OSCC targets and potential treatments.<\/jats:p>","DOI":"10.1002\/mc.70131","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T17:25:09Z","timestamp":1779816309000},"page":"977-988","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["EphA2\/SHP2\/SOX8 Axis: A Novel Target for Regulation of Migration and Cetuximab Treatment Sensitivity in Oral Squamous Cell Carcinoma"],"prefix":"10.1002","volume":"65","author":[{"given":"Dayong","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Stomatology Zhengzhou Central Hospital Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lele","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Stomatology Zhengzhou Central Hospital Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Pei","sequence":"additional","affiliation":[{"name":"Department of Stomatology Zhengzhou Central Hospital Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9882-900X","authenticated-orcid":false,"given":"Ketao","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Stomatology Zhengzhou Central Hospital Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2008.06.002"},{"issue":"12","key":"e_1_2_11_3_1","first-page":"3333","article-title":"Effects of Damnacanthal and Nordamnacanthal on Proliferation, Apoptosis, and Migration of Oral Squamous Cell Carcinoma Cells","volume":"18","author":"Shaghayegh G.","year":"2017","journal-title":"Asian Pacific Journal of Cancer Prevention: APJCP"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.4317\/medoral.18772"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0360-3016(00)01488-7"},{"issue":"6","key":"e_1_2_11_6_1","first-page":"2166","article-title":"Modulation of Radiation Response After Epidermal Growth Factor Receptor Blockade in Squamous Cell Carcinomas: Inhibition of Damage Repair, Cell Cycle Kinetics, and Tumor Angiogenesis","volume":"6","author":"Huang S. 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