{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T15:09:29Z","timestamp":1789744169738,"version":"4.0.1"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273072"],"award-info":[{"award-number":["82273072"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>G protein-coupled receptor 87 (GPR87) has been implicated in the growth and progression of several malignancies, but its role in cutaneous squamous cell carcinoma (cSCC) remains poorly understood. Here, we found that GPR87 was aberrantly upregulated in murine and human skin tumors and in 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated HaCaT keratinocytes. Using a 7,12-dimethylbenz[a]anthracene (DMBA)\/TPA-induced mouse skin tumor model, we demonstrated that GPR87 knockout significantly delayed epidermal hyperplasia, tumor initiation, and malignant progression. Consistently, GPR87 knockdown suppresses TPA-induced keratinocyte proliferation, migration, stemness, and epithelial\u2013mesenchymal transition in keratinocytes and cSCC cells. Mechanistically, GPR87 deficiency markedly reduced SOX2 expression in cultured cells and skin lesions. GPR87 knockdown also enhanced mammalian STE20-like serine\/threonine kinases 1\/2 (MST1\/2) and large tumor suppressor kinases (LATS1\/2) phosphorylation, increased inhibitory YAP phosphorylation, and suppressed Yes-associated protein (YAP) nuclear localization and downstream transcriptional activity. Importantly, activation of YAP by either YAP(S127A) expression or XMU-MP-1 treatment restored SOX2 expression in GPR87-depleted cells, whereas verteporfin-mediated inhibition of YAP\u2013TEA domain transcription factor (TEAD) activity attenuated TPA-induced SOX2 upregulation. Together, these findings identify GPR87 as a key positive regulator of skin tumor initiation and progression and demonstrate that its tumor-promoting effects are mediated, at least in part, through the YAP\u2013SOX2 axis. GPR87 may therefore represent a potential therapeutic target for cSCC.<\/jats:p>","DOI":"10.1093\/carcin\/bgag065","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T11:16:43Z","timestamp":1788520603000},"source":"Crossref","is-referenced-by-count":0,"title":["GPR87 promotes DMBA\/TPA-induced skin tumorigenesis through the YAP\u2013SOX2 axis"],"prefix":"10.1093","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5652-8914","authenticated-orcid":false,"given":"Biao","family":"Guo","sequence":"first","affiliation":[{"name":"Institute of Biomedical Sciences and School of Life Sciences, East China Normal University , Shanghai 200241 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyi","family":"Liang","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences and School of Life Sciences, East China Normal University , Shanghai 200241 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0711-2277","authenticated-orcid":false,"given":"Xiaofeng","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Yangzhi Rehabilitation Hospital, Tongji University , Shanghai 201619 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zile","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences and School of Life Sciences, East China Normal University , Shanghai 200241 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0745-7580","authenticated-orcid":false,"given":"Jiahui","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences and School of Life Sciences, East China Normal University , Shanghai 200241 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoyun","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences and School of Life Sciences, East China Normal University , Shanghai 200241 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0719-748X","authenticated-orcid":false,"given":"Yijing","family":"Ma","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences and School of Life Sciences, East China Normal University , Shanghai 200241 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qidan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences and School of Life Sciences, East China Normal University , Shanghai 200241 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiyun","family":"Ye","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences and School of Life Sciences, East China Normal University , Shanghai 200241 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1618-2916","authenticated-orcid":false,"given":"Yongyan","family":"Dang","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences and School of Life Sciences, East China Normal University , Shanghai 200241 ,","place":["China"]},{"name":"Liwa Institute of Skin Health, East China Normal University , Shanghai 200241 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,6]]},"reference":[{"key":"2026091810540838200_bgag065-B1","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1111\/ijd.16164","article-title":"The risk of metastases from squamous cell carcinoma of the skin","volume":"62","author":"Caudill","year":"2023","journal-title":"Int J Dermatol"},{"key":"2026091810540838200_bgag065-B2","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1007\/s40257-016-0207-3","article-title":"Cutaneous squamous cell carcinoma: a review of high-risk and metastatic disease","volume":"17","author":"Burton","year":"2016","journal-title":"Am J Clin Dermatol"},{"key":"2026091810540838200_bgag065-B3","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1007\/s11864-019-0697-3","article-title":"Epidermal growth factor receptor\u2019s function in cutaneous squamous cell carcinoma and its role as a therapeutic target in the age of immunotherapies","volume":"21","author":"de Lima","year":"2020","journal-title":"Curr Treat Options Oncol"},{"key":"2026091810540838200_bgag065-B4","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1408667","article-title":"Real-world evidence study on the early use of cemiplimab in the UK: REACT-CEMI (real world evidence of advanced CSCC treatment with cemiplimab)","volume":"15","author":"Challapalli","year":"2024","journal-title":"Front Immunol"},{"key":"2026091810540838200_bgag065-B5","doi-asserted-by":"publisher","first-page":"4803","DOI":"10.1007\/s00210-024-03684-6","article-title":"The path of GPR87: from a P2Y-like receptor to its role in cancer progression","volume":"398","author":"Sak","year":"2024","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"2026091810540838200_bgag065-B6","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1038\/nm.3878","article-title":"Genomic landscape of carcinogen-induced and genetically induced mouse skin squamous cell carcinoma","volume":"21","author":"Nassar","year":"2015","journal-title":"Nat Med"},{"key":"2026091810540838200_bgag065-B7","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1186\/s12943-017-0627-6","article-title":"Overexpression of G protein-coupled receptor GPR87 promotes pancreatic cancer aggressiveness and activates NF-\u03baB signaling pathway","volume":"16","author":"Wang","year":"2017","journal-title":"Mol Cancer"},{"key":"2026091810540838200_bgag065-B8","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1038\/s42003-022-03506-6","article-title":"GPR87 promotes tumor cell invasion and mediates the immunogenomic landscape of lung adenocarcinoma","volume":"5","author":"Bai","year":"2022","journal-title":"Commun Biol"},{"key":"2026091810540838200_bgag065-B9","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1038\/s41419-024-06626-5","article-title":"Transglutaminase 3 regulates cutaneous squamous carcinoma differentiation and inhibits progression via PI3K-AKT signaling pathway-mediated keratin 14 degradation","volume":"15","author":"Zhou","year":"2024","journal-title":"Cell Death Dis"},{"key":"2026091810540838200_bgag065-B10","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/3771711","article-title":"TOPK affects autophagy of skin squamous cell carcinoma by regulating NF-KB pathway through HDAC1","volume":"2022","author":"Li","year":"2022","journal-title":"Dis Markers"},{"key":"2026091810540838200_bgag065-B11","doi-asserted-by":"publisher","first-page":"2334","DOI":"10.1016\/j.jid.2022.02.017","article-title":"P2RY6 has a critical role in mouse skin carcinogenesis by regulating the YAP and \u03b2-catenin signaling pathways","volume":"142","author":"Xu","year":"2022","journal-title":"J Invest Dermatol"},{"key":"2026091810540838200_bgag065-B12","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1111\/1346-8138.12104","article-title":"Keratoacanthoma and other types of squamous cell carcinoma with crateriform architecture: classification and identification","volume":"40","author":"Misago","year":"2013","journal-title":"J Dermatol"},{"key":"2026091810540838200_bgag065-B13","doi-asserted-by":"publisher","first-page":"3735","DOI":"10.3892\/ol.2019.10019","article-title":"Silencing of EPHB2 promotes the epithelial-mesenchymal transition of skin squamous cell carcinoma-derived A431 cells","volume":"17","author":"Inagaki","year":"2019","journal-title":"Oncol Lett"},{"key":"2026091810540838200_bgag065-B14","doi-asserted-by":"publisher","first-page":"4511","DOI":"10.1038\/ncomms5511","article-title":"SOX2 is a cancer-specific regulator of tumour initiating potential in cutaneous squamous cell carcinoma","volume":"5","author":"Siegle","year":"2014","journal-title":"Nat Commun"},{"key":"2026091810540838200_bgag065-B15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0061056","article-title":"G protein-coupled receptor 87 (GPR87) promotes the growth and metastasis of CD133+ cancer stem-like cells in hepatocellular carcinoma","volume":"8","author":"Yan","year":"2013","journal-title":"PLoS One"},{"key":"2026091810540838200_bgag065-B16","doi-asserted-by":"publisher","first-page":"19","DOI":"10.3390\/cancers14010019","article-title":"GPR87 promotes metastasis through the AKT-eNOS-NO axis in lung adenocarcinoma","volume":"14","author":"Ahn","year":"2021","journal-title":"Cancers (Basel)"},{"key":"2026091810540838200_bgag065-B17","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1016\/j.omto.2020.01.006","article-title":"G protein-coupled receptor GPR87 promotes the expansion of PDA stem cells through activating JAK2\/STAT3","volume":"17","author":"Jiang","year":"2020","journal-title":"Mol Ther Oncolytics"},{"key":"2026091810540838200_bgag065-B18","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1038\/nature13305","article-title":"SOX2 controls tumour initiation and cancer stem-cell functions in squamous-cell carcinoma","volume":"511","author":"Boumahdi","year":"2014","journal-title":"Nature"},{"key":"2026091810540838200_bgag065-B19","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1111\/j.1365-2443.2010.01400.x","article-title":"Role of SOX2 in maintaining pluripotency of human embryonic stem cells","volume":"15","author":"Adachi","year":"2010","journal-title":"Genes Cells"},{"key":"2026091810540838200_bgag065-B20","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.1111\/exd.14655","article-title":"Targeting the Hippo\/YAP\/TAZ signalling pathway: novel opportunities for therapeutic interventions into skin cancers","volume":"31","author":"Howard","year":"2022","journal-title":"Exp Dermatol"},{"key":"2026091810540838200_bgag065-B21","doi-asserted-by":"publisher","first-page":"135","DOI":"10.5021\/ad.23.156","article-title":"Emerging perspectives of YAP\/TAZ in human skin epidermal and dermal aging","volume":"36","author":"Kim","year":"2024","journal-title":"Ann Dermatol"},{"key":"2026091810540838200_bgag065-B22","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.33304","article-title":"YAP drives cutaneous squamous cell carcinoma formation and progression","volume":"7","author":"Vincent-Mistiaen","year":"2018","journal-title":"Elife"},{"key":"2026091810540838200_bgag065-B23","doi-asserted-by":"publisher","first-page":"1556","DOI":"10.1158\/1541-7786.Mcr-18-0158","article-title":"YAP tyrosine phosphorylation and nuclear localization in cholangiocarcinoma cells are regulated by LCK and independent of LATS activity","volume":"16","author":"Sugihara","year":"2018","journal-title":"Mol Cancer Res"},{"key":"2026091810540838200_bgag065-B24","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.devcel.2014.06.003","article-title":"The hippo pathway effector yap controls patterning and differentiation of airway epithelial progenitors","volume":"30","author":"Mahoney","year":"2014","journal-title":"Dev Cell"},{"key":"2026091810540838200_bgag065-B25","doi-asserted-by":"publisher","first-page":"1705","DOI":"10.1002\/stem.1993","article-title":"YAP1 regulates OCT4 activity and SOX2 expression to facilitate self-renewal and vascular mimicry of stem-like cells","volume":"33","author":"Bora-Singhal","year":"2015","journal-title":"Stem Cells"}],"container-title":["Carcinogenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/carcin\/advance-article-pdf\/doi\/10.1093\/carcin\/bgag065\/70969108\/bgag065.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/carcin\/article-pdf\/47\/3\/bgag065\/70969108\/bgag065.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/carcin\/article-pdf\/47\/3\/bgag065\/70969108\/bgag065.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T14:54:13Z","timestamp":1789743253000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/carcin\/article\/doi\/10.1093\/carcin\/bgag065\/8786288"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":25,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,7,7]]}},"URL":"https:\/\/doi.org\/10.1093\/carcin\/bgag065","relation":{},"ISSN":["0143-3334","1460-2180"],"issn-type":[{"value":"0143-3334","type":"print"},{"value":"1460-2180","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026]]},"published":{"date-parts":[[2026]]},"article-number":"bgag065"}}