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(Landmark Ed)"],"abstract":"<jats:p>Background:Tazarotene-induced gene 2 (TIG2), also known as retinoic acid receptor responder 2 (RARRES2), encodes the secreted protein TIG2, also known as chemerin, which is involved in immune regulation and metabolism. However, its role in melanoma remains unclear. Methods:TIG2 expression was analyzed using The Cancer Genome Atlas, Genotype-Tissue Expression, OncoDB, and melanoma tissue cDNA arrays. To evaluate its effects on cell viability and death, TIG2 was overexpressed in A2058 and A375 melanoma cells. RNA sequencing (RNA-seq), qPCR, and Western blotting were performed to identify TIG2-regulated genes and signaling pathways. The involvement of chemokines and endoplasmic reticulum (ER) stress was further examined using the C-X-C motif chemokine ligand 10 (CXCL 10)\/CXCL11 and the ER stress inhibitor tauroursodeoxycholic acid (TUDCA).Results:TIG2 expression was reduced in melanoma and other skin cancers. TIG2 overexpression significantly reduced cell viability and induced cell death. RNA-seq analysis showed that TIG2 downregulated CXCL10, CXCL11, and CCL2 while upregulating ER stress-related genes such as HERPUD1 and DDIT3. Exogenous CXCL10 or CXCL11 did not reverse TIG2-mediated effects, whereas TUDCA partially restored cell viability and reduced cell death.Conclusions:These findings suggest that TIG2 suppresses melanoma cell growth by activating ER stress and modulating immune-related chemokines, highlighting its potential therapeutic relevance.<\/jats:p>","DOI":"10.31083\/fbl54095","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:35:31Z","timestamp":1788438931000},"source":"Crossref","is-referenced-by-count":0,"title":["Tazarotene-Induced Gene 2 Promotes Melanoma Cell Death via the Activation of Endoplasmic Reticulum Stress"],"prefix":"10.31083","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8527-980X","authenticated-orcid":true,"given":"Chun-Hua","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Dermatology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, 231 New Taipei City, Taiwan"},{"name":"School of Medicine, Tzu Chi University, 970 Hualien, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8708-0792","authenticated-orcid":true,"given":"Lu-Kai","family":"Wang","sequence":"additional","affiliation":[{"name":"National Center for Biomodels, National Institutes of Applied Research, 115 Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4563-0458","authenticated-orcid":true,"given":"Fu-Ming","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, 231 New Taipei City, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Nagpal S, Patel S, Jacobe H, DiSepio D, Ghosn C, Malhotra M, et al. 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