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However, the mechanisms underlying activation and maintenance of OCSLC stemness remain unclear. Here, it is identified an increased expression of peptidylarginine deiminase 1 (PAD1) in OC cells, particularly within the CD133\n                    <jats:sup>+<\/jats:sup>\n                    subset or cisplatin\u2010resistant cells, which is positively associated with the upregulation of stemness\u2010related markers and maintenance of stemness in OCSLCs. Mechanistically, PAD1 specifically binds to the kinase domain of AKT2 and catalyzes citrullination at R202. Citrullination subsequently promotes AKT2 phosphorylation at S474 and T309, the two critical residues for AKT2 kinase activity. As a major driver of OC malignancy, the activation of AKT2 leads to an increased expression of CCAAT\/Enhancer Binding Protein Beta\u00a0(CEBP\u03b2), thereby promoting CEBP\u03b2 enrichment to the promoters of a subset of stemness\u2010related genes. Moreover, PAD1 gene silencing, inhibition of AKT2 citrullination, and AKT2 mutation all decrease the tumor\u2010initiating ability of OC cells both in vitro and in vivo. Importantly, treatment with a PAD1 inhibitor can resensitize cisplatin\u2010resistant OC cells to cisplatin treatment, suggesting that targeting PAD1\/AKT2\/CEBP\u03b2 signaling axis in OCSLCs may be highly effective in preventing OC progression.\n                  <\/jats:p>","DOI":"10.1002\/advs.202501014","type":"journal-article","created":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T04:45:32Z","timestamp":1755924332000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Citrullination of AKT2 Catalyzed by PAD1 Facilitates the Maintenance of Stemness Characteristics of Ovarian Cancer Stem\u2010Like Cells in Ovarian Cancer"],"prefix":"10.1002","volume":"12","author":[{"given":"Teng","family":"Xue","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology College of Basic Medical Science China Medical University  Shenyang 110122 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqiu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology College of Basic Medical Science China Medical University  Shenyang 110122 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Song","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine Nanjing Medical University  Nanjing 211166 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujia","family":"Fei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine Nanjing Medical University  Nanjing 211166 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Gu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine Nanjing Medical University  Nanjing 211166 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Science China Medical University  Shenyang 110122 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul R","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Pharmacology University of Massachusetts Medical School  Worcester MA 01655 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8877-1536","authenticated-orcid":false,"given":"Xuesen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology College of Basic Medical Science China Medical University  Shenyang 110122 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