{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T01:08:37Z","timestamp":1793236117562,"version":"4.5.0"},"reference-count":30,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T00:00:00Z","timestamp":1726012800000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,9,1]],"date-time":"2024-09-01T00:00:00Z","timestamp":1725148800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2018MH013"],"award-info":[{"award-number":["ZR2018MH013"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2023MH040"],"award-info":[{"award-number":["ZR2023MH040"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771554"],"award-info":[{"award-number":["81771554"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81471437"],"award-info":[{"award-number":["81471437"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Epithelial ovarian cancer is the deadliest gynecologic malignancy, characterized by high metastasis. Transforming growth factor\u2010\u03b21 (TGF\u2010\u03b21) drives epithelial\u2010 mesenchymal transformation (EMT), a key process in tumor metastasis. Tumor necrosis factor\u2010\u03b1\u2010induced protein 8 (TNFAIP8)\u2010like 2 (TIPE2) acts as a negative regulator of innate and adaptive immunity and involves in various cancers. However, its relationship with TGF\u2010\u03b21 in ovarian cancer and its role in reversing TGF\u2010\u03b21\u2010induced EMT remain unclear. This study examined TIPE2 mRNA and protein expression using quantitative RT\u2010PCR (qRT\u2010PCR), western blot and immunohistochemistry. The effects of TIPE2 overexpression and knockdown on the proliferation, migration and invasion of epithelial ovarian cancer cells were assessed through 5\u2010ethynyl\u20102\u2010deoxyuridine, colony\u2010forming, transwell migration and invasion assays. The relationship between TIPE2 and TGF\u2010\u03b21 was investigated using qRT\u2010PCR and enzyme\u2010linked immunosorbent assay, while the interaction between TIPE2 and Smad2 was identified via co\u2010immunoprecipitation. The results revealed that TIPE2 protein was significantly down\u2010regulated in epithelial ovarian cancer tissues and correlated with the pathological type of tumor, patients' age, tumor differentiation degree and FIGO stage. TIPE2 and TGF\u2010\u03b21 appeared to play an opposite role to each other during the progression of human ovarian cancer cells. Furthermore, TIPE2 inhibited the metastasis and EMT of ovarian cancer cells by combining with Smad2 in\u00a0vitro or in an intraperitoneal metastasis model. Consequently, these findings suggest that TIPE2 plays a crucial inhibitory role in ovarian cancer metastasis by modulating the TGF\u2010\u03b21\/Smad2\/EMT signaling pathway and may serve as a potential target for ovarian cancer, providing important direction for future diagnostic and therapeutic strategies.<\/jats:p>","DOI":"10.1096\/fj.202401427r","type":"journal-article","created":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T11:31:02Z","timestamp":1726054262000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["<scp>TIPE2<\/scp>\n                    inhibits the migration and invasion of epithelial ovarian cancer cells by targeting Smad2 to reverse\n                    <scp>TGF<\/scp>\n                    \u2010\u03b21\u2010induced\n                    <scp>EMT<\/scp>"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3655-7110","authenticated-orcid":false,"given":"Zhongyun","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine Shandong University  Jinan Shandong P.R. 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