{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:57:45Z","timestamp":1791565065234,"version":"4.3.4"},"reference-count":29,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100022298","name":"Hualien Tzu Chi Hospital","doi-asserted-by":"crossref","award":["TCRD 113-050"],"award-info":[{"award-number":["TCRD 113-050"]}],"id":[{"id":"10.13039\/501100022298","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100022298","name":"Hualien Tzu Chi Hospital","doi-asserted-by":"crossref","award":["TCMF-CP 114-01"],"award-info":[{"award-number":["TCMF-CP 114-01"]}],"id":[{"id":"10.13039\/501100022298","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100022298","name":"Hualien Tzu Chi Hospital","doi-asserted-by":"crossref","award":["NSTC 112-2314-B-303-010-MY3"],"award-info":[{"award-number":["NSTC 112-2314-B-303-010-MY3"]}],"id":[{"id":"10.13039\/501100022298","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Advanced-stage ovarian cancer remains a major clinical challenge because of its aggressive behavior and the frequent development of chemoresistance. The nuclear factor erythroid-derived 2\u2013like 2 (NRF2) signaling pathway regulates cellular redox homeostasis. However, its role in ovarian cancer stem-like cells remains unclear. Therefore, we aimed to investigate the effects of NRF2 overexpression on acetaldehyde dehydrogenase (ALDH)+ KURAMOCHI ovarian cancer cells in vitro and in vivo. In particular, we investigated the effects of NRF2 on tumor-associated behaviors, chemoresistance, and signaling pathways. Lentivirus-mediated NRF2 overexpression activated extracellular signal-regulated kinase and AKT signaling. Moreover, it modulated tumor-associated phenotypes, including proliferation, migration, and invasion. NRF2-overexpressing cells exhibited significantly enhanced migratory and invasive capacities, increased resistance to paclitaxel and carboplatin, and reduced apoptosis. Furthermore, the expression of anti-apoptotic proteins was upregulated, and caspase-3 activation was attenuated. In xenograft models, NRF2 overexpression promoted tumor growth and increased the expression of antioxidant and angiogenic factors, including heme oxygenase-1 and vascular endothelial growth factor A. Collectively, these findings demonstrate that NRF2 regulates ovarian cancer aggressiveness and chemoresistance by coordinating stress response signaling, survival pathways, and tumor progression. Therefore, targeting NRF2-mediated signaling represents a promising therapeutic strategy for overcoming drug resistance and improving outcomes in patients with ovarian cancer.<\/jats:p>","DOI":"10.3390\/ijms27062820","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T10:49:58Z","timestamp":1774003798000},"page":"2820","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["NRF2 Drives Aggressiveness and Chemoresistance in Ovarian Cancer Stem-like Cells"],"prefix":"10.3390","volume":"27","author":[{"given":"Yu-Hsun","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-Hung","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dah-Ching","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien 970, Taiwan"},{"name":"Institute of Medical Sciences, Tzu Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,20]]},"reference":[{"key":"ref_1","first-page":"7","article-title":"Cancer Statistics, 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA Cancer J. 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