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In breast cancer patients, elevated expression of cartilage oligomeric matrix protein (COMP) is associated with shorter survival and increased metastatic risk. Here, we investigated the role of COMP in regulating EMT in breast cancer. Breast cancer cells treated with recombinant COMP or engineered to overexpress\n                    <jats:italic>COMP<\/jats:italic>\n                    exhibited a marked decrease in the epithelial marker\n                    <jats:italic>CDH1<\/jats:italic>\n                    and an increase in mesenchymal markers such as\n                    <jats:italic>VIM<\/jats:italic>\n                    and\n                    <jats:italic>VCAN<\/jats:italic>\n                    . Consistent with these\n                    <jats:italic>in vitro<\/jats:italic>\n                    findings,\n                    <jats:italic>COMP<\/jats:italic>\n                    \u2010expressing xenograft tumor tissues showed enhanced EMT characteristics. Functionally, COMP promoted increased migration and invasion of breast cancer cells in both autocrine and paracrine manners, dependent on its thrombospondin (TSP) and C\u2010terminal domains. We further identified protein TMEPAI (encoded by gene\n                    <jats:italic>PMEPA1<\/jats:italic>\n                    ) as a functional COMP\u2010binding partner that mediates COMP\u2010induced EMT, primarily through interaction with the TSP domain of COMP. Mechanistically, COMP shifted transforming growth factor beta (TGF\u03b2) signaling from canonical phosphorylated mothers against decapentaplegic homolog 2\/3 (pSMAD2\/3) activation toward pSMAD1\/5, likely through its interaction with PMEPA1. This study suggests the COMP\u2013PMEPA1 axis as a new driver of EMT in breast cancer models.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.70221","type":"journal-article","created":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T07:19:17Z","timestamp":1771053557000},"page":"1780-1799","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>COMP<\/scp>\n                    \u2013\n                    <scp>PMEPA1<\/scp>\n                    axis promotes epithelial\u2010to\u2010mesenchymal transition in breast cancer cells"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5834-1447","authenticated-orcid":false,"given":"Konstantinos S.","family":"Papadakos","sequence":"first","affiliation":[{"name":"Division of Medical Protein Chemistry, Department of Translational Medicine Lund University  Malm\u00f6 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