{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:25:49Z","timestamp":1792095949494,"version":"4.4.0"},"reference-count":31,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Grant-in-Aid for Scientific Research, JSPS KAKENHI (C)","award":["24K10460"],"award-info":[{"award-number":["24K10460"]}]},{"name":"Promotion and Mutual Aid Corporation for Private Schools of Japan","award":["24K10460"],"award-info":[{"award-number":["24K10460"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>CD26 (dipeptidyl peptidase-4) is a marker of colorectal cancer stem cells with high metastatic potential and resistance to therapy. Although CD26 expression is known to be associated with tumor progression, its functional involvement in epithelial-mesenchymal transition (EMT) and metastasis remains to be fully elucidated. In this study, we aimed to investigate the effects of a monoclonal anti-CD26 antibody on EMT-related phenotypes and metastatic behavior in colorectal cancer cells. We evaluated changes in EMT markers by quantitative PCR and Western blotting, assessed cell motility and invasion using scratch wound-healing and Transwell assays, and examined metastatic potential in vivo using a splenic injection mouse model. Treatment with the anti-CD26 antibody significantly increased the expression of the epithelial marker E-cadherin and reduced levels of EMT-inducing transcription factors, including ZEB1, Twist1, and Snail1, at the mRNA and protein levels. Functional assays revealed that the antibody markedly inhibited cell migration and invasion in vitro without exerting cytotoxic effects. Furthermore, systemic administration of the anti-CD26 antibody significantly suppressed the formation of liver metastases in vivo. These findings suggest that CD26 may contribute to the regulation of EMT and metastatic behavior in colorectal cancer. Our data highlight the potential therapeutic utility of CD26-targeted antibody therapy for suppressing EMT-associated phenotypes and metastatic progression.<\/jats:p>","DOI":"10.3390\/ijms26157620","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T15:09:53Z","timestamp":1754492993000},"page":"7620","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Anti-CD26 Antibody Suppresses Epithelial-Mesenchymal Transition in Colorectal Cancer Stem Cells"],"prefix":"10.3390","volume":"26","author":[{"given":"Takumi","family":"Iwasawa","sequence":"first","affiliation":[{"name":"Shizuoka Medical Research Center for Disaster, Juntendo University, 1129 Nagaoka Izunokuni, Shizuoka 410-2295, Japan"},{"name":"Institute of Life Innovation Studies, Toyo University, Tokyo 115-8650, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2727-7275","authenticated-orcid":false,"given":"Ryo","family":"Hatano","sequence":"additional","affiliation":[{"name":"Department of Therapy Development and Innovation for Immune Disorders and Cancers, Juntendo University, 2-1-1 Hongo Bunkyo Ward, Tokyo 113-8421, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Takeda","sequence":"additional","affiliation":[{"name":"Shizuoka Medical Research Center for Disaster, Juntendo University, 1129 Nagaoka Izunokuni, Shizuoka 410-2295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayumi","family":"Kurusu","sequence":"additional","affiliation":[{"name":"Shizuoka Medical Research Center for Disaster, Juntendo University, 1129 Nagaoka Izunokuni, Shizuoka 410-2295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chikako","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Shizuoka Medical Research Center for Disaster, Juntendo University, 1129 Nagaoka Izunokuni, Shizuoka 410-2295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazunori","family":"Kato","sequence":"additional","affiliation":[{"name":"Institute of Life Innovation Studies, Toyo University, Tokyo 115-8650, Japan"},{"name":"Atopy Research Center, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo Bunkyo Ward, Tokyo 113-8421, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chikao","family":"Morimoto","sequence":"additional","affiliation":[{"name":"Department of Therapy Development and Innovation for Immune Disorders and Cancers, Juntendo University, 2-1-1 Hongo Bunkyo Ward, Tokyo 113-8421, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriaki","family":"Iwao","sequence":"additional","affiliation":[{"name":"Shizuoka Medical Research Center for Disaster, Juntendo University, 1129 Nagaoka Izunokuni, Shizuoka 410-2295, Japan"},{"name":"Division of Blood Transfusion, Juntendo Shizuoka Hospital, 1129 Nagaoka Izunokuni, Shizuoka 410-2295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,6]]},"reference":[{"key":"ref_1","first-page":"17","article-title":"Cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA Cancer J. 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