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In the present study, we investigated the expression and function of DPP4 in androgen-sensitive and castration-resistant prostate cancer (CRPC) models. Proteomic analysis of androgen-resistant prostate cells overexpressing DPP4 identified the involvement of the cellular adhesion molecules pathway. In prostate cells, lentiviral-mediated DPP4 overexpression restored androgen receptor signaling, inhibited epithelial-to-mesenchymal transition, and reduced cell migration, whereas DPP4 silencing produced the opposite effects. We demonstrate that DPP4 expression is down-regulated in CRPC cells and that treatment with capsaicin (CAP), a bioactive compound derived from red peppers, restores DPP4 expression. Moreover, DPP4 restoration by CAP suppresses prostate tumorigenesis in the TRAMP mice in vivo model of prostate cancer. Our results suggest that DPP4 could be a new target for CRPC.<\/jats:p>","DOI":"10.1042\/bsr20260054","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:08:28Z","timestamp":1787562508000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Proteomic profiling reveals that DPP4 overexpression increases cell adhesion, inhibits cell migration, and restores androgen sensitivity in prostate cancer"],"prefix":"10.1042","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0831-8067","authenticated-orcid":false,"given":"Jos\u00e9\u00a0Mar\u00eda","family":"Mora-Rodr\u00edguez","sequence":"first","affiliation":[{"name":"1University of Alcal\u00e1, School of Medicine and Health Sciences, Department of Systems Biology, Biochemistry and Molecular Biology Unit, 28871 Alcal\u00e1 de Henares, Madrid, Spain"},{"name":"2Health Research Institute of Castilla-La Mancha (IDISCAM), Toledo, Castilla-La Mancha, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0971-1522","authenticated-orcid":false,"given":"Bel\u00e9n\u00a0G.","family":"S\u00e1nchez","sequence":"additional","affiliation":[{"name":"1University of Alcal\u00e1, School of Medicine and Health Sciences, Department of Systems Biology, Biochemistry and Molecular Biology Unit, 28871 Alcal\u00e1 de Henares, Madrid, Spain"},{"name":"2Health Research Institute of Castilla-La Mancha (IDISCAM), Toledo, Castilla-La Mancha, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1490-5823","authenticated-orcid":false,"given":"Alicia","family":"Bort","sequence":"additional","affiliation":[{"name":"1University of Alcal\u00e1, School of Medicine and Health Sciences, Department of Systems Biology, Biochemistry and Molecular Biology Unit, 28871 Alcal\u00e1 de Henares, Madrid, Spain"},{"name":"2Health Research Institute of Castilla-La Mancha (IDISCAM), Toledo, Castilla-La Mancha, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alba","family":"D\u00edaz-Yuste","sequence":"additional","affiliation":[{"name":"3Institute of Food Science Research, CIAL (CSIC-UAM), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Milla","sequence":"additional","affiliation":[{"name":"1University of Alcal\u00e1, School of Medicine and Health Sciences, Department of Systems Biology, Biochemistry and Molecular Biology Unit, 28871 Alcal\u00e1 de Henares, Madrid, Spain"},{"name":"2Health Research Institute of Castilla-La Mancha (IDISCAM), Toledo, Castilla-La Mancha, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Courraud","sequence":"additional","affiliation":[{"name":"4Section of Clinical Therapeutics, Department of Medicine, National and Kapodistrian University of Athens, Alexandra Hospital, Athens, Greece"},{"name":"5Proteomics Core Facility, School of Science, National and Kapodistrian University of Athens, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerome","family":"Zoidakis","sequence":"additional","affiliation":[{"name":"6Section of Biochemistry and Molecular Biology, Department of Biology, National and Kapodistrian University of Athens, Athens, Greece"},{"name":"7Proteomics Laboratory, Biomedical Research Foundation, Academy of Athens, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9704-4373","authenticated-orcid":false,"given":"In\u00e9s","family":"D\u00edaz-Laviada","sequence":"additional","affiliation":[{"name":"1University of Alcal\u00e1, School of Medicine and Health Sciences, Department of Systems Biology, Biochemistry and Molecular Biology Unit, 28871 Alcal\u00e1 de Henares, Madrid, Spain"},{"name":"2Health Research Institute of Castilla-La Mancha (IDISCAM), Toledo, Castilla-La Mancha, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"key":"2026090402264986300_B1","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3322\/caac.21871","article-title":"Cancer statistics, 2025","volume":"75","author":"Siegel","year":"2025","journal-title":"CA Cancer J. 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