{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T17:05:33Z","timestamp":1790183133319,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":7,"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"}],"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>\n                    Cutaneous squamous cell carcinoma (cSCC) is among the most common epithelial malignancies. Although cSCC arising in long\u2010standing acne inversa (AI) lesions is rare, it is a severe and clinically important complication of AI. Approximately one\u2010third of patients with AI harbour loss\u2010of\u2010function mutations in\n                    <jats:italic>NCSTN<\/jats:italic>\n                    . Whether NCSTN loss contributes to cSCC development remains unclear. To address this, we first examined its expression pattern in cSCC tissues. Interestingly, NCSTN expression was significantly decreased in cSCC tissues by immunohistochemistry (IHC) and Western blotting. Furthermore, loss of NCSTN promoted cSCC cell proliferation and migration in\u00a0vitro and tumour growth in\u00a0vivo. Proteomic analysis revealed that NCSTN deficiency promoted cell proliferation through activation of the MAPK\/ERK signalling pathway, accompanied by reduced CLDN3 expression and alterations in cell\u2010adhesion\u2010related pathways. To validate the functional relevance of this signalling axis in\u00a0vivo, we treated NCSTN\u2010knockdown tumour\u2010bearing mice with the ERK inhibitor SCH772984, which effectively suppressed tumour growth. Collectively, these findings demonstrate that loss of NCSTN drives cSCC progression through activation of MAPK\/ERK signalling, and identify ERK signalling as a potential therapeutic vulnerability in NCSTN\u2010deficient cSCC.\n                  <\/jats:p>","DOI":"10.1111\/exd.70350","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:48:11Z","timestamp":1788932891000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nicastrin Regulates Cutaneous Squamous Cell Carcinoma Progression Through the\n                    <scp>MAPK<\/scp>\n                    \/\n                    <scp>ERK<\/scp>\n                    Signalling"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1828-0257","authenticated-orcid":false,"given":"Shumeng","family":"Xue","sequence":"first","affiliation":[{"name":"Jiangsu Provincial Key Laboratory of Dermatology, Hospital 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