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Immunol."],"abstract":"<jats:p>\n                    Abrine, an indole alkaloid, was evaluated for its anti-metastatic activity and mechanism in non-small cell lung cancer (NSCLC) models. Human A549 and H1975 cells were exposed to Abrine, showing no cytotoxicity but marked suppression of TGF-\u03b21-induced migration and invasion by scratch and Transwell assays. Mechanistically, Abrine reversed epithelial-mesenchymal transition (EMT) by upregulating E-cadherin and reducing N-cadherin, vimentin, Snail and Slug, findings corroborated by immunofluorescence. Abrine also diminished phosphorylation of ERK, JNK and p38 while modulating the Nrf2\/Keap-1\/HO-1 axis. Target engagement was supported by molecular docking, CETSA, DARTS, and MST indicating specific binding and thermal stabilization of ERK.\n                    <jats:italic>In vivo<\/jats:italic>\n                    , Abrine (20 or 40 mg\/kg) mitigated lung metastasis in a B16-F10 intravenous model, improving body weight, decreasing lung metastatic burden, lung wet weight and lung index, and reducing Ki67 expression in lung tissue. Systemic effects included lowered circulating IL-17, IL-10, TNF-\u03b1 and IFN-\u03b3, and absence of overt histopathological toxicity in major organs. Combination with the ERK1\/2 inhibitor SCH772984 further enhanced efficacy. Collectively, Abrine exerts potent anti-metastatic effects by directly targeting ERK to inhibit MAPK signaling, reversing EMT and engaging the Nrf2\/Keap-1\/HO-1 pathway, highlighting Abrine alone or with ERK inhibition as a promising therapeutic strategy against lung metastasis model.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1789110","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T06:40:26Z","timestamp":1774593626000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Abrine targets ERK to suppress EMT and lung metastasis model via MAPKs and Nrf2\/Keap-1\/HO-1 signaling"],"prefix":"10.3389","volume":"17","author":[{"given":"Yufang","family":"Shen","sequence":"first","affiliation":[{"name":"Guangxi University of Chinese Medicine, Traditional Chinese Medicine Zhuang Yao Drug Innovation Drug Engineering Research Center","place":["Nanning, China"]},{"name":"College 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