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The mechanisms that drive canine OMM metastasis are still largely unknown, providing for limited therapeutic approaches once the disease has spread to metastatic sites. The objective of this investigation was to evaluate the differences in gene expression between canine primary OMMs and their matched nodal metastases. Transcriptional profiling of formalin-fixed, paraffin-embedded biopsies of 4 canine OMMs and their respective lymph node biopsies was performed using exon microarrays. Confirmation of the differential expression of selected genes was subsequently sought by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) on 13 paired samples (primary tumor-metastatic lymph node). Results highlight the activation of pathways associated with actin cytoskeleton organization, and cellular motility and migration. In particular, transcriptional data indicated increased expression of genes associated with Rac1 signaling-regulated cell migration, including\n                    <jats:italic toggle=\"yes\">ELMO1, VAV3<\/jats:italic>\n                    , and\n                    <jats:italic toggle=\"yes\">DOCK2<\/jats:italic>\n                    , in nodal metastases. Overall, the results of this investigation point to a significant role for Rac1 signaling in the pathogenesis of OMM metastasis to regional lymph nodes. The Rac1 signaling\u2013associated genes highlighted herein are indeed involved in the activation of cellular migration, and one, or more, may represent a future therapeutic target to prevent metastatic dissemination, or treat OMM with distant metastases.\n                  <\/jats:p>","DOI":"10.1177\/03009858251386913","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T06:19:59Z","timestamp":1764310799000},"page":"193-203","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Rac1 signaling\u2013associated genes are upregulated in nodal metastasis of canine oral mucosal melanoma"],"prefix":"10.1177","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9466-3918","authenticated-orcid":false,"given":"Stefano","family":"Di Palma","sequence":"first","affiliation":[{"name":"IDEXX, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2882-6739","authenticated-orcid":false,"given":"Ilaria","family":"Porcellato","sequence":"additional","affiliation":[{"name":"University of Perugia, Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1040-6245","authenticated-orcid":false,"given":"Camilla","family":"Capaccia","sequence":"additional","affiliation":[{"name":"University of Perugia, Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3695-9275","authenticated-orcid":false,"given":"Gabriella","family":"Guelfi","sequence":"additional","affiliation":[{"name":"University of Perugia, Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriana","family":"Lo Giudice","sequence":"additional","affiliation":[{"name":"University of Perugia, Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4812-3216","authenticated-orcid":false,"given":"Chiara","family":"Brachelente","sequence":"additional","affiliation":[{"name":"University of Perugia, Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8667-5070","authenticated-orcid":false,"given":"Wilhelmina","family":"Bergmann","sequence":"additional","affiliation":[{"name":"Utrecht University Faculty of Veterinary Medicine, Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2694-905X","authenticated-orcid":false,"given":"Barbara","family":"Brunetti","sequence":"additional","affiliation":[{"name":"University of Bologna, Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mike","family":"Starkey","sequence":"additional","affiliation":[{"name":"Wellcome Sanger Institute, Hinxton, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"key":"e_1_3_2_2_2","unstructured":"Affymetrix Exon and Gene Array Glossary. 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