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Overexpressed of MMSA-1\u2019s interaction with RAS protein and its downstream signaling pathways was investigated. Moreover, the interaction changes between overexpressed MMSA-1 protein and bone marrow microenvironment were also detected by examing adhesion molecules and angiogenesis promoting factors using Western Blot.\u00a0We successfully constructed\n                    <jats:italic>transcription factor 4 (TCF4)<\/jats:italic>\n                    and\n                    <jats:italic>MMSA-1<\/jats:italic>\n                    over\/down expressed stable U266 cell lines (termed\n                    <jats:sup>\n                      <jats:italic>TCF4\u2212\/+<\/jats:italic>\n                    <\/jats:sup>\n                    U266 and\n                    <jats:sup>\n                      <jats:italic>MMSA\u22121\u2212\/+<\/jats:italic>\n                    <\/jats:sup>\n                    U266). Our result showed that\n                    <jats:italic>TCF4<\/jats:italic>\n                    could bind with\n                    <jats:italic>MMSA-1<\/jats:italic>\n                    promoter sequence, greatly up regulate its promotor activity and then improve\n                    <jats:italic>MMSA-1<\/jats:italic>\n                    expression. Overexpressed\n                    <jats:italic>MMSA-1<\/jats:italic>\n                    also made a series of changes in U266 cells, including promoting RAS protein expression in cytoplasm, enhancing the interaction between\n                    <jats:italic>MMSA-1<\/jats:italic>\n                    and\n                    <jats:italic>RAS<\/jats:italic>\n                    , which resulted in hyperactivation of RAS and its downstream signaling pathways including RAF\/MEK\/ERK and RAF\/PI3K\/AKT, improving U266 cells\u2019 clonogenicity capacity, changing apoptosis related proteins, reducing the interaction between myeloma cell and bone marrow microenvironment by reducing adhesion molecules expression including HIF-1\u03b1, E-cadherin, CXCR4 expression and elevating angiogenesis promoting factors including VEGF, Ang-2 and reducing Ang-1 at the same time.\u00a0These results suggested\n                    <jats:italic>MMSA-1<\/jats:italic>\n                    was over expressed in MM cells being regulated by\n                    <jats:italic>Wnt\/\u03b2-catenin\/TCF4<\/jats:italic>\n                    signaling pathway, which resulted in hyperactivation of downstream RAS\/RAF signaling pathway and eventually promote myeloma cells survival and invasion.\n                  <\/jats:p>","DOI":"10.1007\/s00277-026-06740-8","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T01:39:42Z","timestamp":1768441182000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MMSA-1 is regulated by Wnt\/TCF4 and involved in multiple myeloma progression and invasion via RAS\/RAF signaling pathway"],"prefix":"10.1007","volume":"105","author":[{"given":"Shan","family":"Meng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hailing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liufang","family":"Gu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianli","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanhong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,15]]},"reference":[{"key":"6740_CR1","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.clml.2019.03.025","volume":"19","author":"T Martin","year":"2019","unstructured":"Martin T, Huff CA (2019) Multiple myeloma: current advances and future directions. 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