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As one of the factors causing skin dryness is a decrease in sebum production due to sebaceous gland dysfunction, we examined whether vemurafenib regulated the production and accumulation of sebum in hamster sebocytes. Vemurafenib dose\u2010 and time\u2010dependently decreased the production and accumulation of sebum in DHT\u2010differentiated hamster sebocytes. In addition, the DHT\u2010augmented gene expressions of SCD\u20101, DGAT\u20101 and PLIN\u20101, which are involved in sebum production and accumulation in sebaceous glands, were suppressed by vemurafenib in hamster sebocytes. Unexpectedly, vemurafenib facilitated ERK phosphorylation in hamster sebocytes. In addition, DHT augmented the phosphorylation of ERK, under which vemurafenib synergistically enhanced the DHT\u2010augmented phosphorylation. The enhanced ERK phosphorylation was no longer detectable by adding an ERK inhibitor, U0126. On the other hand, as mTOR plays an important role in the regulation of sebum production, the phosphorylation of Akt and 4EBP1, which are the upstream and downstream molecules in mTOR signalling, respectively, was increased in the DHT\u2010treated hamster sebocytes. Vemurafenib inhibited the DHT\u2010augmented 4EBP1 phosphorylation, which was no longer detectable in the presence of U0126. Furthermore, the suppression of the DHT\u2010augmented sebum production and accumulation by vemurafenib was restored to their levels in DHT alone upon the U0126 treatment. Thus, these results provide novel evidence that vemurafenib suppresses sebum production and accumulation by the vemurafenib\u2010activated ERK signalling that inhibits the Akt\/mTOR pathway in DHT\u2010differentiated hamster sebocytes.<\/jats:p>","DOI":"10.1111\/exd.70150","type":"journal-article","created":{"date-parts":[[2025,8,16]],"date-time":"2025-08-16T07:19:54Z","timestamp":1755328794000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Suppression of Sebum Production by Vemurafenib Through Paradoxical <scp>ERK<\/scp> Activation Resulted in the Inhibition of the <scp>mTOR<\/scp> Pathway in 5\u03b1\u2010Dihydrotestosterone\u2010Differentiated Hamster Sebocytes In\u00a0Vitro"],"prefix":"10.1111","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9847-8931","authenticated-orcid":false,"given":"Toshikazu","family":"Koiwai","sequence":"first","affiliation":[{"name":"Department of Biochemistry Tokyo University of Pharmacy and Life Sciences  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0687-9696","authenticated-orcid":false,"given":"Takashi","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Tokyo University of Pharmacy and Life Sciences  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,16]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2015.3"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/17460441.2016.1201057"},{"issue":"3","key":"e_1_2_9_4_1","first-page":"331","article-title":"Management of Dermatologic Toxicities Associated With Targeted Therapy","volume":"7","author":"Lacouture M. 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