{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:13:37Z","timestamp":1786119217193,"version":"build-2736575974"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Triple\u2010negative breast cancer (TNBC) is an aggressive subtype that is characterized by a high metastatic capacity, limited therapeutic options, and a poor prognosis, largely because of its stemness properties and aberrant signaling. Dynorphin A, an endogenous opioid peptide, has been identified as a potential modulator of cancer progression, although its role in TNBC remains unclear. This study demonstrates that the Dynorphin\/\u03ba\u2010opioid receptor (KOR) signaling axis is markedly diminished in TNBC patients and TNBC cell lines, suggesting its tumor\u2010suppressive function. Functional assays revealed that Dynorphin A suppresses TNBC cell proliferation, migration, invasion, and stemness while inducing apoptosis. Cell cycle analysis showed Dynorphin A induced G1\/S phase arrest. Mechanistically, Dynorphin A blocked epithelial\u2212mesenchymal transition (EMT) by restoring E\u2010cadherin and reducing N\u2010cadherin, Vimentin, and Snail. Morphological analysis confirmed a reversion from mesenchymal to epithelial phenotype. Furthermore, it attenuated stem cell\u2010like properties as indicated by lower levels of CD44, CD133, and Octamer\u2010binding transcription factor 4 (OCT4). Notably, Dynorphin A disrupted zinc finger E\u2010box binding homeobox 1 (ZEB1)\u2010mediated Wnt\/\u03b2\u2010catenin signaling, and forced expression of ZEB1 partially rescued \u03b2\u2010catenin levels, confirming that ZEB1 is a downstream mediator. These findings identify Dynorphin A as a promising endogenous inhibitor of TNBC progression that targets both malignancy and stemness via the ZEB1\/\u03b2\u2010catenin axis.<\/jats:p>","DOI":"10.1002\/ddr.70232","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T07:01:37Z","timestamp":1770102097000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dynorphin A Inhibits the Proliferation, Migration, Invasion, and Stemness of Triple Negative Breast Cancer Cells"],"prefix":"10.1002","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6103-7946","authenticated-orcid":false,"given":"Xiaojiao","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Breast and Thyroid Surgery, Sichuan Gemflower Hospital North Sichuan Medical College Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Breast and Thyroid Surgery, Sichuan Gemflower Hospital North Sichuan Medical College Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Breast and Thyroid Surgery, Sichuan Gemflower Hospital North Sichuan Medical College Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengyun","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Breast and Thyroid Surgery, Sichuan Gemflower Hospital North Sichuan Medical College Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Breast and Thyroid Surgery, Sichuan Gemflower Hospital North Sichuan Medical College Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Breast and Thyroid Surgery, Sichuan Gemflower Hospital North Sichuan Medical College Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12131809"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2025.119408"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-023-11362-8"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-018-4985-6"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2023.03.077"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201400668"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1255820"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2015.05.010"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9061511"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.4103\/ccd.ccd_252_20"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI45014"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.24875\/RIC.23000256"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2019.172787"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11203294"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-020-00387-2"},{"issue":"7","key":"e_1_2_9_17_1","first-page":"3208","article-title":"Research Progress in Breast Cancer Stem Cells: Characterization and Future Perspectives","volume":"12","author":"Mao X. 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