{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:10:18Z","timestamp":1789171818427,"version":"build-2803163510"},"reference-count":54,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100011264","name":"FP7 People: Marie-Curie Actions","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["\u200e1990\/18"],"award-info":[{"award-number":["\u200e1990\/18"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["888\/24 \u200e"],"award-info":[{"award-number":["888\/24 \u200e"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:p>\n                    Paired box protein Pax\u20108 (\n                    <jats:italic>PAX8<\/jats:italic>\n                    ) is a critical lineage marker and master regulator of transcription in high\u2010grade serous ovarian carcinoma (HGSC)\u2014the most common subtype of epithelial ovarian cancer\u2014driving cell proliferation and migration and resisting apoptosis. This study aimed to elucidate the mechanism of action of PAX8 in this disease. By performing an unbiased analysis of PAX8\u2010regulated genes, we discovered two PAX8\u2010regulated genes\u2014coiled\u2010coil domain\u2010containing protein 80 (\n                    <jats:italic>CCDC80<\/jats:italic>\n                    ) and cluster of differentiation 276 (\n                    <jats:italic>CD276<\/jats:italic>\n                    ) antigen (also known as B7\u2010H3)\u2014that mediate PAX8 activity and play key cancer cell autonomous roles in this disease. Our findings indicate that PAX8 negatively regulates\n                    <jats:italic>CCDC80<\/jats:italic>\n                    , a novel cell autonomous tumor suppressor in HGSC. We demonstrate that CCDC80, localized to the nucleus, significantly reduces HGSC tumor growth and metastasis\n                    <jats:italic>in vivo<\/jats:italic>\n                    in a mouse model. Notably, CCDC80 exerts its function by suppressing the expression of the immune checkpoint protein B7\u2010H3. However, in HGSC, B7\u2010H3 is predominantly cytoplasmic and promotes HGSC proliferation and migration independent of its immune role. Additionally, PAX8 positively regulates\n                    <jats:italic>B7\u2010H3<\/jats:italic>\n                    expression in a CCDC80\u2010independent manner, underscoring the multifaceted oncogenic role of PAX8. This study highlights the complex regulatory network involving PAX8, CCDC80, and B7\u2010H3 in HGSC progression. Targeting this signaling pathway may provide a novel therapeutic strategy to improve treatment outcomes for patients with epithelial ovarian cancer. B7\u2010H3, which is currently targeted in clinical trials, shows promise as HGSC target for therapy.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.70235","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T09:47:12Z","timestamp":1776764832000},"page":"2262-2279","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>CCDC80<\/scp>\n                    suppresses high\u2010grade serous ovarian cancer migration via negative regulation of\n                    <scp>B7<\/scp>\n                    \u2010\n                    <scp>H3<\/scp>"],"prefix":"10.1002","volume":"20","author":[{"given":"Aya","family":"Saleh","sequence":"first","affiliation":[{"name":"Division of Oncology, Clinical Research Institute at Rambam Rambam Health Care Campus  Haifa Israel"},{"name":"Women's Cancers Research Lab, Ruth and Bruce Rappaport Faculty of Medicine Technion \u2010 Israel Institute of 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