{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T05:05:36Z","timestamp":1784091936318,"version":"3.55.0"},"reference-count":32,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T00:00:00Z","timestamp":1783728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of University and Research","award":["DM 737\/2021"],"award-info":[{"award-number":["DM 737\/2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Epithelial\u2013mesenchymal transition (EMT) emerged as a phenotypic change associated with the resistance to epidermal growth factor receptor tyrosine kinase inhibitors, both in vitro and in vivo. The mechanisms underlying this biological process have not yet been fully understood. E-cadherin loss, N-cadherin, and vimentin increase are the main markers characterizing EMT, together with the expression of some transcription factors, such as Snail, Slug, Zeb1, Zeb2, and Twist. In this study, we explore the expression of these markers in lung cancer cell lines bearing wild-type or mutated epidermal growth factor receptor (EGFR), A549 and PC9, respectively. We treated PC9 cells with Gefitinib or Osimetinib, alone or combined with the transforming growth factor beta (TGF-\u03b2). We evaluated the expression of E-cadherin, N-cadherin, vimentin, and the transcription factors at 24 and 96 h timepoints, to verify the role of EMT in the early phases of the treatment with tyrosine kinase inhibitors (TKIs). At the 96 h timepoint, we found that in PC9 cells, the treatment with gefitinib or osimertinib, regardless of TGF-\u03b2, induces E-cadherin reduction and N-cadherin increase, similar to the effects induced by TGF-\u03b2 in A549 cells at 24 h. Among the transcription factors, at 96 h, Slug mainly increases when PC9 cells are treated with gefitinib or osimertinib. These results imply that changes in the expression of these epithelial\u2013mesenchymal transition markers may have facilitated the development of drug resistance.<\/jats:p>","DOI":"10.3390\/ijms27146207","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T08:53:58Z","timestamp":1783932838000},"page":"6207","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Early-Phase Activation of Epithelial\u2013Mesenchymal Transition in Lung Cancer Cells Treated with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors"],"prefix":"10.3390","volume":"27","author":[{"given":"Alessia","family":"Belloni","sequence":"first","affiliation":[{"name":"Department of Clinical and Molecular Sciences (DISCLIMO), Polytechnic University of Marche, 60121 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9324-4765","authenticated-orcid":false,"given":"Lorenza","family":"Tamberi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Sciences (DISCLIMO), Polytechnic University of Marche, 60121 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1874-5217","authenticated-orcid":false,"given":"Laura","family":"Graciotti","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Public Health, Polytechnic University of Marche, 60121 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0887-4453","authenticated-orcid":false,"given":"Tatiana","family":"Spadoni","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Public Health, Polytechnic University of Marche, 60121 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1840-3903","authenticated-orcid":false,"given":"Giulia","family":"Matacchione","sequence":"additional","affiliation":[{"name":"Clinic of Laboratory and Precision Medicine, National Institute of Health and Sciences on Ageing (IRCCS INRCA), 60127 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1733-654X","authenticated-orcid":false,"given":"Chiara","family":"Giordani","sequence":"additional","affiliation":[{"name":"Clinic of Laboratory and Precision Medicine, National Institute of Health and Sciences on Ageing (IRCCS INRCA), 60127 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8477-8519","authenticated-orcid":false,"given":"Angelica","family":"Giuliani","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Sciences (DISCLIMO), Polytechnic University of Marche, 60121 Ancona, Italy"},{"name":"Clinic of Laboratory and Precision Medicine, National Institute of Health and Sciences on Ageing (IRCCS INRCA), 60127 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5373-3636","authenticated-orcid":false,"given":"Elisa","family":"Chiadini","sequence":"additional","affiliation":[{"name":"Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6624-7730","authenticated-orcid":false,"given":"Laura","family":"Capelli","sequence":"additional","affiliation":[{"name":"Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Donno","sequence":"additional","affiliation":[{"name":"Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Sbrighi","sequence":"additional","affiliation":[{"name":"Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Zanoni","sequence":"additional","affiliation":[{"name":"Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Ulivi","sequence":"additional","affiliation":[{"name":"Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Rita","family":"Rippo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Sciences (DISCLIMO), Polytechnic University of Marche, 60121 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucio","family":"Crin\u00f2","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, IRCCS Istituto Romagnolo Per Lo Studio Dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9768-7149","authenticated-orcid":false,"given":"Matteo","family":"Canale","sequence":"additional","affiliation":[{"name":"Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2306-2445","authenticated-orcid":false,"given":"Giuseppe","family":"Bronte","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Sciences (DISCLIMO), Polytechnic University of Marche, 60121 Ancona, Italy"},{"name":"Clinic of Laboratory and Precision Medicine, National Institute of Health and Sciences on Ageing (IRCCS INRCA), 60127 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1126\/science.1073096","article-title":"Cancer. 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