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However, the intricate mechanisms underlying breast cancer metastasis driven by deregulated splicing events remain largely unexplored. Here, we unveiled that RBM7 is decreased in lymph node and distant organ metastases of breast cancer as compared to primary lesions and low expression of RBM7 is correlated with the reduced disease-free survival of breast cancer patients. Breast cancer cells with RBM7 depletion exhibited an increased potential for lung metastasis compared to scramble control cells. The absence of RBM7 stimulated breast cancer cell migration, invasion, and angiogenesis. Mechanistically, RBM7 controlled the splicing switch of MFGE8, favoring the production of the predominant isoform of MFGE8, MFGE8-L. This resulted in the attenuation of STAT1 phosphorylation and alterations in cell adhesion molecules. MFGE8-L exerted an inhibitory effect on the migratory and invasive capability of breast cancer cells, while the truncated isoform MFGE8-S, which lack the second F5\/8 type C domain had the opposite effect. In addition, RBM7 negatively regulates the NF-\u03baB cascade and an NF-\u03baB inhibitor could obstruct the increase in HUVEC tube formation caused by RBM7 silencing. Clinically, we noticed a positive correlation between RBM7 expression and MFGE8 exon7 inclusion in breast cancer tissues, providing new mechanistic insights for molecular-targeted therapy in combating breast cancer.<\/jats:p>","DOI":"10.7554\/elife.95318","type":"journal-article","created":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T13:25:05Z","timestamp":1708694705000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.95318","source":"Crossref","is-referenced-by-count":11,"title":["RBM7 deficiency promotes breast cancer metastasis by coordinating MFGE8 splicing switch and NF-kB pathway"],"prefix":"10.7554","volume":"13","author":[{"given":"Fang","family":"Huang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04c8eg608","id-type":"ROR","asserted-by":"publisher"}],"name":"Sino-US Research Center for Cancer Translational Medicine of the Second Affiliated Hospital of Dalian Medical University & Institute of Cancer Stem Cell, Dalian Medical 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