{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:20:16Z","timestamp":1791994816606,"version":"4.4.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Faced with the highly malignant threat of metastatic triple-negative breast cancer (TNBC), the effect of traditional chemical agents is limited, and new anti-metastasis drug remains to be explored. Celastrol (Cel) is a bioactive compound derived from\n                    <jats:italic>Tripterygium wilfordii<\/jats:italic>\n                    with significant anti-neoplastic effects in various cancers. In this study, we investigated the potential anti-metastatic effects of Cel on anoikis resistant TNBC cells (TNBC-AR) cells, including MDA-MB-231-AR cells and BT-549-AR cells. Using CCK-8 and colony formation assay, we demonstrated that Cel could inhibit the proliferation of MDA-MB-231-AR cells and BT-549-AR cells with IC\n                    <jats:sub>50<\/jats:sub>\n                    value of 1.510\u00a0\u03bcM and 1.673\u00a0\u03bcM, respectively. The results of wound healing and transwell assays showed that Cel could potently inhibit the invasion and migration of TNBC-AR cells. Aggregation and flow cytometry experiments showed that Cel could inhibit the clusters formation and enhance the anoikis of TNBC-AR cells on the suspension conditions. Then we conducted bioinformatics analysis, Western blotting, and intervention experiments to explore the molecular mechanisms of Cel\u2019s anti-metastasis effects. The results of these experiments discovered that Cel treatment suppressed the p-EMT state in TNBC-AR cells, and this effect correlated with a reduction in EGFR\/MEK\/ERK pathway activation. Our findings suggest that Cel may be a promising candidate for therapeutic treatments of metastatic TNBC.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2026.1747871","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T06:37:09Z","timestamp":1772433429000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Celastrol increases anoikis sensitivity to suppress triple-negative breast cancer via EGFR pathway and p-EMT state regulation"],"prefix":"10.3389","volume":"17","author":[{"given":"Jue","family":"Yang","sequence":"first","affiliation":[{"name":"School of Materia Medica, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangpeng","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Materia Medica, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuyun","family":"Bai","sequence":"additional","affiliation":[{"name":"School of Materia Medica, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongjun","family":"Deng","sequence":"additional","affiliation":[{"name":"School of Materia Medica, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanting","family":"Ye","sequence":"additional","affiliation":[{"name":"School of Materia Medica, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiqiong","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Materia Medica, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Xing","sequence":"additional","affiliation":[{"name":"School of Materia Medica, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxing","family":"Yao","sequence":"additional","affiliation":[{"name":"School of Materia Medica, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiping","family":"Lyu","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, Hong Kong Baptist University","place":["Kowloon, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Lu","sequence":"additional","affiliation":[{"name":"Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyan","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Materia Medica, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"127","DOI":"10.3390\/life15010127","article-title":"Navigating the collective: nanoparticle-assisted identification of leader cancer cells during migration","volume":"15","author":"Alexandrova","year":"2025","journal-title":"Life"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e156057","DOI":"10.1172\/jci.insight.156057","article-title":"Stabilization of E-cadherin adhesions by COX-2\/GSK3\u03b2 signaling is a targetable pathway in metastatic breast cancer","volume":"8","author":"Balamurugan","year":"2023","journal-title":"JCI Insight"},{"key":"B3","doi-asserted-by":"publisher","first-page":"4588","DOI":"10.3390\/ijms26104588","article-title":"Ergosterol peroxide disrupts triple-negative breast cancer mitochondrial function and inhibits tumor growth and metastasis","volume":"26","author":"Bocachica-Adorno","year":"2025","journal-title":"Int. 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