{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:36:25Z","timestamp":1787027785138,"version":"build-2736575974"},"reference-count":70,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T00:00:00Z","timestamp":1661731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Associazione Italiana per la Ricerca sul Cancro (AIRC)","award":["IG 18387"],"award-info":[{"award-number":["IG 18387"]}]},{"name":"Associazione Italiana per la Ricerca sul Cancro (AIRC)","award":["IG 25024"],"award-info":[{"award-number":["IG 25024"]}]},{"name":"Associazione Italiana per la Ricerca sul Cancro (AIRC)","award":["2017ZXT5WR"],"award-info":[{"award-number":["2017ZXT5WR"]}]},{"name":"PRIN (Progetti di rilevante interesse nazionale)-MIUR","award":["IG 18387"],"award-info":[{"award-number":["IG 18387"]}]},{"name":"PRIN (Progetti di rilevante interesse nazionale)-MIUR","award":["IG 25024"],"award-info":[{"award-number":["IG 25024"]}]},{"name":"PRIN (Progetti di rilevante interesse nazionale)-MIUR","award":["2017ZXT5WR"],"award-info":[{"award-number":["2017ZXT5WR"]}]},{"name":"Ricerca per Credere nella vita (R.C.V.)","award":["IG 18387"],"award-info":[{"award-number":["IG 18387"]}]},{"name":"Ricerca per Credere nella vita (R.C.V.)","award":["IG 25024"],"award-info":[{"award-number":["IG 25024"]}]},{"name":"Ricerca per Credere nella vita (R.C.V.)","award":["2017ZXT5WR"],"award-info":[{"award-number":["2017ZXT5WR"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Multiple myeloma (MM) is a malignant plasma cell (PC) neoplasm, which also displays pathological bone involvement. Clonal expansion of MM cells in the bone marrow causes a perturbation of bone homeostasis that culminates in MM-associated bone disease (MMABD). We previously demonstrated that the S\/T kinase CK1\u03b1 sustains MM cell survival through the activation of AKT and \u03b2-catenin signaling. CK1\u03b1 is a negative regulator of the Wnt\/\u03b2-catenin cascade, the activation of which promotes osteogenesis by directly stimulating the expression of RUNX2, the master gene regulator of osteoblastogenesis. In this study, we investigated the role of CK1\u03b1 in the osteoblastogenic potential of mesenchymal stromal cells (MSCs) and its involvement in MM\u2013MSC cross-talk. We found that CK1\u03b1 silencing in in vitro co-cultures of MMs and MSCs modulated RUNX2 expression differently in PCs and in MSCs, mainly through the regulation of Wnt\/\u03b2-catenin signaling. Our findings suggest that the CK1\u03b1\/RUNX2 axis could be a potential therapeutic target for constraining malignant PC expansion and supporting the osteoblastic transcriptional program of MSCs, with potential for ameliorating MMABD. Moreover, considering that Lenalidomide treatment leads to MM cell death through Ikaros, Aiolos and CK1\u03b1 proteasomal degradation, we examined its effects on the osteoblastogenic potential of MSC compartments.<\/jats:p>","DOI":"10.3390\/cancers14174173","type":"journal-article","created":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T21:01:31Z","timestamp":1661806891000},"page":"4173","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["CK1\u03b1\/RUNX2 Axis in the Bone Marrow Microenvironment: A Novel Therapeutic Target in Multiple Myeloma"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1291-542X","authenticated-orcid":false,"given":"Anna","family":"Fregnani","sequence":"first","affiliation":[{"name":"Hematology and Clinical Immunology Branch, Department of Medicine, University of Padova, 35128 Padova, Italy"},{"name":"Laboratory of Myeloma and Lymphoma Pathobiology, 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Branca","sequence":"additional","affiliation":[{"name":"Hematology and Clinical Immunology Branch, Department of Medicine, University of Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmela","family":"Gurrieri","sequence":"additional","affiliation":[{"name":"Hematology and Clinical Immunology Branch, Department of Medicine, University of Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8799-5324","authenticated-orcid":false,"given":"Renato","family":"Zambello","sequence":"additional","affiliation":[{"name":"Hematology and Clinical Immunology Branch, Department of Medicine, University of Padova, 35128 Padova, Italy"},{"name":"Laboratory of Myeloma and Lymphoma Pathobiology, Veneto Institute of Molecular Medicine (VIMM), 35129 Padova, 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