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This study aimed to characterize the mode of action of tirbanibulin in keratinocytes (NHEK) and cutaneous squamous cell carcinoma (cSCC) cell lines (A431, SCC-12) in vitro. Tirbanibulin significantly reduced proliferation in a dose-dependent manner in all investigated cell lines, inhibited migration, and induced G2\/M-cell cycle arrest only in the cSCC cell lines analyzed, and induced apoptosis solely in A431, which showed the highest sensitivity to tirbanibulin. In general, we detected low basal expression of phosphorylated SRC in all cell lines analyzed, therefore, interference with SRC signaling does not appear to be the driving force regarding the observed effects of tirbanibulin. The most prominent tirbanibulin-mediated effect was on \u03b2-tubulin-polymerization, which was especially impaired in A431. Additionally, tirbanibulin induced an increase of the proinflammatory cytokines IL-1\u03b1, bFGF and VEGF in A431. In conclusion, tirbanibulin mediated anti-tumor effects predominantly in A431, while healthy keratinocytes and more dedifferentiated SCC-12 were less influenced. These effects of tirbanibulin are most likely mediated via dysregulation of \u03b2-tubulin-polymerization and may be supported by proinflammatory aspects.<\/jats:p>","DOI":"10.1007\/s00403-024-03032-x","type":"journal-article","created":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T15:01:48Z","timestamp":1717772508000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Anti-tumor effects of tirbanibulin in squamous cell carcinoma cells are mediated via disruption of tubulin-polymerization"],"prefix":"10.1007","volume":"316","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6246-8862","authenticated-orcid":false,"given":"Viola K.","family":"DeTemple","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5970-7755","authenticated-orcid":false,"given":"Antje","family":"Walter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0950-8323","authenticated-orcid":false,"given":"Sabine","family":"Bredemeier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7921-2820","authenticated-orcid":false,"given":"Ralf","family":"Gutzmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5318-0039","authenticated-orcid":false,"given":"Katrin","family":"Schaper-Gerhardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,7]]},"reference":[{"issue":"6","key":"3032_CR1","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1016\/j.abd.2019.10.004","volume":"94","author":"CPH Reinehr","year":"2019","unstructured":"Reinehr CPH, Bakos RM (2019) Actinic keratoses: review of clinical, dermoscopic, and therapeutic aspects. 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DeTemple received a research grant, honoraria for talks and travel support from SUN Pharma. Katrin Schaper-Gerhardt received a research grant from Almirall and Kyowa Kirin. Ralf Gutzmer served as consultant for BristolMyers Squibb, Roche Pharma, MerckSharpDohme, Novartis, GlaxoSmithKline, Amgen, Almirall Hermal, LEO, Pfizer, Incyte, Pierre-Fabre, Sun Pharma. Ralf Gutzmer received honoraria for lectures from BristolMyers Squibb, Roche Pharma, MerckSharpDohme, Novartis, Amgen, Merck Serono, Almirall-Hermal, Pierre-Fabre, Sanofi, SUN Pharma, Bayer. Ralf Gutzmer received travel support from BristolMyers Squibb, Merck Serono, SUN Pharma, Roche Pharma. Ralf Gutzmer received research grants from Pfizer, Novartis, Johnson&Johnson, Sanofi, Merck Serono, Amgen, SUN Pharma. The other authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"341"}}