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The challenges posed by tumor metastasis and treatment resistance significantly complicate disease management and substantially reduce survival rates. Thus, elucidating the mechanisms underlying ovarian cancer metastasis is crucial for developing targeted therapies and improving patient outcomes. In this study, through single-nucleus RNA sequencing and analysis of clinical samples, we identify PABPC3 as a key regulator of ovarian cancer metastasis and patient survival. Functional experiments reveal that\n                    <jats:italic>PABPC3<\/jats:italic>\n                    knockdown markedly inhibits ovarian cancer cell proliferation and migration, whereas its overexpression exerts the opposite effects. Furthermore, in vivo models confirm that\n                    <jats:italic>PABPC3<\/jats:italic>\n                    overexpression significantly enhances metastatic potential. Mechanistically,\n                    <jats:italic>PABPC3<\/jats:italic>\n                    promotes tumor metastasis by modulating the expression of CLDN1, a critical component of tight junctions.\n                    <jats:italic>PABPC3<\/jats:italic>\n                    knockdown leads to a significant upregulation of CLDN1, while simultaneous CLDN1 knockdown partially rescues the migration-inhibitory effects induced by\n                    <jats:italic>PABPC3<\/jats:italic>\n                    depletion. Additionally, clinical analyses demonstrate that high\n                    <jats:italic>PABPC3<\/jats:italic>\n                    expression correlates with shorter overall survival, even among patients receiving chemotherapy. Notably, increased PABPC3 protein levels in metastatic lesions are associated with reduced progression-free survival. In conclusion, this study underscores the pivotal role of PABPC3 in ovarian cancer metastasis and patient prognosis, highlighting it as a potential therapeutic target for improving clinical outcomes.\n                  <\/jats:p>","DOI":"10.1038\/s41419-025-08151-5","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T15:41:31Z","timestamp":1763394091000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["PABPC3 drives ovarian cancer metastasis and drug sensitivity by downregulating CLDN1 expression"],"prefix":"10.1038","volume":"16","author":[{"given":"Hong","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiping","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mintao","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhan","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haisheng","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangshuang","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7865-765X","authenticated-orcid":false,"given":"Zhisen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9838-8493","authenticated-orcid":false,"given":"Yinyin","family":"Shu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoni","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjuan","family":"Gan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youguo","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7864-0428","authenticated-orcid":false,"given":"Yuhong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5220-7391","authenticated-orcid":false,"given":"Zhe","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingchuan","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9336-9912","authenticated-orcid":false,"given":"Chunlin","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2288-1748","authenticated-orcid":false,"given":"Lei","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,17]]},"reference":[{"key":"8151_CR1","doi-asserted-by":"publisher","first-page":"972","DOI":"10.6004\/jnccn.2022.0047","volume":"20","author":"DK Armstrong","year":"2022","unstructured":"Armstrong DK, Alvarez RD, Backes FJ, Bakkum-Gamez JN, Barroilhet L, Behbakht K, et al. 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