{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T17:05:42Z","timestamp":1790183142095,"version":"4.1.0"},"reference-count":60,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100007225","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST 110\u20102314\u2010B\u2010195\u2010024 \u2010"],"award-info":[{"award-number":["MOST 110\u20102314\u2010B\u2010195\u2010024 \u2010"]}],"id":[{"id":"10.13039\/100007225","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004861","name":"Mackay Memorial Hospital","doi-asserted-by":"publisher","award":["MMH110\u201099"],"award-info":[{"award-number":["MMH110\u201099"]}],"id":[{"id":"10.13039\/501100004861","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Spleen tyrosine kinase (Syk) regulates immune responses and has been implicated in haematopoietic and epithelial cancers. Although our previous studies showed that Syk modulates keratinocyte differentiation and UVB\u2010induced inflammation, its role in UVB\u2010related cutaneous squamous cell carcinoma (cSCC) remains unclear. Tumour necrosis factor\u2010related apoptosis\u2010inducing ligand (TRAIL) selectively induces apoptosis in cancer cells and is expressed in healthy skin but reduced in non\u2010melanoma skin cancers and sun\u2010exposed skin. This study investigated the role of Syk in cSCC and TRAIL\u2010induced apoptosis. Immunohistochemistry revealed elevated phosphorylated and total Syk levels in SCC tissues compared with normal skin. In SCC12 cells, TRAIL induced dose\u2010dependent apoptosis, which was enhanced by pharmacological Syk inhibition or Syk silencing. Combination treatment with TRAIL and Syk inhibitors increased annexin V positivity and cleavage of caspase\u20103, PARP1 and Bid, accompanied by reduced Mcl\u20101 expression. Mechanistically, TRAIL induced Src and Syk phosphorylation. TRAIL\u2010induced Syk activation was suppressed by Src inhibition but not by EGFR inhibition, indicating that Syk activation is Src\u2010dependent but EGFR\u2010independent in this pathway. Syk inhibition further reduced TRAIL\u2010activated Akt and MAPK signalling, while Akt activation may play a role in regulating SCC12 survival. These results suggest that targeting Syk sensitizes TRAIL\u2010mediated apoptosis and may offer a promising therapeutic strategy for treating cutaneous SCC.<\/jats:p>","DOI":"10.1111\/exd.70344","type":"journal-article","created":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T03:10:57Z","timestamp":1789787457000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Syk Inhibition Sensitizes Skin Squamous Carcinoma Cells to\n                    <scp>TRAIL<\/scp>\n                    \u2010Induced Apoptosis"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6596-5706","authenticated-orcid":false,"given":"Po\u2010Hsuan","family":"Lu","sequence":"first","affiliation":[{"name":"School of Medicine, College of Medicine MacKay Medical University  New Taipei City Taiwan"},{"name":"Department of Dermatology MacKay Memorial Hospital  Taipei 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