NSrp70 suppresses metastasis in triple-negative breast cancer by modulating Numb/TβR1/EMT axis

NSrp70 suppresses metastasis in triple-negative breast cancer by modulating Numb/TβR1/EMT axis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article NSrp70 suppresses metastasis in triple-negative breast cancer by modulating Numb/TβR1/EMT axis Yang Zhao, Hefen Sun, Yuanyuan Zhao, Qiqi Liu, Yang Liu, Yifeng Hou, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-311222/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Metastasis is a major cause of death in individuals suffering from triple-negative breast cancer. Alternative splicing of mRNA precursor allows cancer cells to create different protein isoforms which may promote metastasis. Quantitative proteomic analysis of primary and metastatic breast cancer cells revealed that nuclear speckle-related protein 70 (NSrp70) was significantly downregulated in highly metastatic cells. Downregulation of NSrp70 promoted the migration and invasion of breast cancer cells in vitro and in vivo. Mechanistically, we found that NSrp70 inhibited the skipped exon alternative splicing of NUMB, promoted the degradation of TGF-beta receptor 1(TβR1) through lysosome pathway, and regulated TGFβ/SMAD-mediated epithelial-mesenchymal transition (EMT) phenotype in breast cancer cells. Furthermore, high NSrp70 expression correlated with better prognosis in breast cancer patients. Our findings revealed that splicing regulator NSrp70 may serve as a metastasis suppressor. Cancer Biology Oncology NSrp70 alternative splicing breast cancer metastasis TGFβ signaling Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Full Text Additional Declarations There is NO Competing Interest. Supplementary Files AdditionalFiles.docx Additional Files Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-311222","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":17054046,"identity":"dddf1c3a-6b96-4a9e-b398-5dd5a0f84b4d","order_by":0,"name":"Yang Zhao","email":"","orcid":"","institution":"Fudan University Shanghai Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yang","middleName":"","lastName":"Zhao","suffix":""},{"id":17054047,"identity":"649910a3-fc2a-4761-92a6-521d4e34db47","order_by":1,"name":"Hefen Sun","email":"","orcid":"","institution":"Department of Breast Surgery, Fudan University 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alternative splicing, breast cancer, metastasis, TGFβ signaling","lastPublishedDoi":"10.21203/rs.3.rs-311222/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-311222/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eMetastasis is a major cause of death in individuals suffering from triple-negative breast cancer. 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