{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T10:33:18Z","timestamp":1776853998903,"version":"3.51.2"},"reference-count":54,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,8,17]],"date-time":"2024-08-17T00:00:00Z","timestamp":1723852800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Integrins, the receptors of the extracellular matrix, are critical in the proliferation and metastasis of cancer cells. GMI, a Ganoderma microsporum immunomodulatory protein, possesses anticancer and antivirus abilities. The object of this study is to investigate the role of GMI in the integrins signaling pathway in lung cancer cells that harbor the EGFR L858R\/T790M double mutation and osimertinib\u2010resistance. Liquid chromatography\u2010mass spectrometry and western blot assay were used to investigate the effect of GMI on inhibiting the protein expressions of integrins in H1975 cells. The migration ability and xenograft tumor growth of H1975 were suppressed by GMI. To elucidate the role of the integrin family in lung cancer resistant to osimertinib (AZD\u20109291, Tagrisso), H1975 cells were used to establish the osimertinib\u2010resistant cells, named H1975\/TR cells. The expressions of Integrin \u03b1V and stemness markers were much higher in H1975\/TR cells than in H1975 cells. GMI suppressed cell viability, tumor spheroid growth, and the expressions of integrin \u03b1V and \u03b21 in H1975\/TR cells. Furthermore, GMI suppressed the expressions of stemness markers and formation of tumor spheres via blocking integrin \u03b1V signaling cascade. This is the first study to reveal the novel function of GMI in constraining cancer stem cells and migration by abolishing the integrin \u03b1V\u2010related signaling pathway in EGFR\u2010mutated and osimertinib\u2010resistant lung cancer cells.<\/jats:p>","DOI":"10.1002\/tox.24399","type":"journal-article","created":{"date-parts":[[2024,8,17]],"date-time":"2024-08-17T09:29:37Z","timestamp":1723886977000},"page":"5238-5249","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Integrin <scp>\u03b1V<\/scp> Inhibition by <scp>GMI<\/scp>, a Ganoderma Microsporum Immunomodulatory Protein, Abolish Stemness and Migration in <scp>EGFR<\/scp>\u2010Mutated Lung Cancer Cells Resistant to Osimertinib"],"prefix":"10.1002","volume":"39","author":[{"given":"Yu\u2010Ting","family":"Kang","sequence":"first","affiliation":[{"name":"Institute of Medicine Chung Shan Medical University  Taichung Taiwan"},{"name":"Department of Medical 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