{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:39:51Z","timestamp":1790361591045,"version":"4.1.0"},"reference-count":66,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Health Trust Fund of the Scottish Terrier Club of America"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Metastasis-associated protein 1 (MTA1), an oncogenic transcriptional regulator, is overexpressed in canine urothelial carcinoma (UC) and is associated with aggressive clinicopathological features. However, its functional role and molecular mechanisms in canine UC remain poorly understood. Here, we investigated the contribution of MTA1 to epithelial-to-mesenchymal transition (EMT) and its interaction with BRAF signaling. MTA1 silencing in two canine UC cell lines significantly inhibited cell proliferation, cell survival, migration, and xenograft tumor growth. Mechanistically, MTA1 knockdown reduced the expression of MTA2, MTA3, and COX2, while producing unexpected changes in key EMT regulators, including Snail, Slug, and Cyclin D1, suggesting the activation of compensatory signaling pathways. MTA1 silencing also decreased mutant BRAF expression in AxA cells while increasing wild-type BRAF expression in SH cells, indicating context-dependent regulation of BRAF signaling. In AxA cells, reduced AKT phosphorylation following MTA1 knockdown further supports functional crosstalk between the BRAF and MTA1\/AKT signaling pathways. Collectively, these findings identify MTA1 as a critical regulator of canine UC progression and reveal complex signaling interactions that support its potential as a therapeutic target for canine UC.<\/jats:p>","DOI":"10.3390\/ijms27167272","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T11:57:46Z","timestamp":1786708666000},"page":"7272","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["MTA1 Regulates EMT and BRAF Signaling Networks in Canine Urothelial Carcinoma"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3946-0066","authenticated-orcid":false,"given":"Gisella","family":"Campanelli","sequence":"first","affiliation":[{"name":"Department of Veterinary Biomedical Sciences, Lewyt College of Veterinary Medicine, Long Island University, Brookville, NY 11548, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nema","family":"Parkhomovsky","sequence":"additional","affiliation":[{"name":"Lewyt College of Veterinary Medicine, Long Island University, Brookville, NY 11548, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3188-7453","authenticated-orcid":false,"given":"Chun Kuen","family":"Mak","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Sciences, Lewyt College of Veterinary Medicine, Long Island University, Brookville, NY 11548, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biomedical Sciences, Lewyt College of Veterinary Medicine, Long Island University, Brookville, NY 11548, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0646-2575","authenticated-orcid":false,"given":"Anait S.","family":"Levenson","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biomedical Sciences, Lewyt College of Veterinary Medicine, Long Island University, Brookville, NY 11548, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1093\/ilar\/ilu018","article-title":"Urinary bladder cancer in dogs, a naturally occurring model for cancer biology and drug development","volume":"55","author":"Knapp","year":"2014","journal-title":"ILAR J."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Brambilla, E., Govoni, V.M., Cavalca, A.M.B., Laufer-Amorim, R., Fonseca-Alves, C.E., and Grieco, V. 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