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In this study, we hypothesized that cyclins D might have additional roles in the pathogenesis of MM beyond cell cycle control. We showed that overexpression of\n                    <jats:italic>CCND1<\/jats:italic>\n                    and\n                    <jats:italic>CCND2<\/jats:italic>\n                    in MM cell lines lacking these proteins revealed a mutually exclusive expression pattern, with both cyclins D localized in the cytoplasm and no impact on proliferation. To investigate non\u2010canonical roles of cyclin D1, we performed transcriptome analysis and multidimensional flow cytometry. Cyclin D1 overexpression led to upregulation of several key cell adhesion pathway proteins, including STAT1 and ZO\u20101, along with alterations in the actin cytoskeleton and decreased adhesion to certain matrices. Immunophenotypic analysis showed a significant reduction in CD56 expression following cyclin D1 overexpression, validated in a cohort of 85\u2009MM patients, in which 73% with high cyclin D1 were CD56\u2010negative. High cyclin D1 was also associated with increased circulating tumor cells (CTCs) (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001). Overall, we revealed novel functions of cyclin D1 in MM pathogenesis, particularly in cell adhesion and dissemination.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.70085","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T16:50:03Z","timestamp":1752771003000},"page":"3175-3192","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Exploring the role of cyclin\n                    <scp>D1<\/scp>\n                    in the pathogenesis of multiple myeloma beyond cell cycle regulation"],"prefix":"10.1002","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6772-6859","authenticated-orcid":false,"given":"Ignacio J.","family":"Cardona\u2010Benavides","sequence":"first","affiliation":[{"name":"Hematology Department, Institute of Biomedical Research of Salamanca (IBSAL) University Hospital of Salamanca  Spain"},{"name":"Cancer Research Center\u2010IBMCC 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