Pauperization of Emerin from nuclear envelope during chromatin bridge resolution drives prostate cancer cell migration and invasiveness

Pauperization of Emerin from nuclear envelope during chromatin bridge resolution drives prostate cancer cell migration and invasiveness | 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 Pauperization of Emerin from nuclear envelope during chromatin bridge resolution drives prostate cancer cell migration and invasiveness Paulina Nastaly, Marta Popęda, Kamil Kowalski, Tomasz Wenta, Galina Beznoussenko, and 14 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3533837/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 02 Sep, 2024 Read the published version in Experimental & Molecular Medicine → Version 1 posted You are reading this latest preprint version Abstract Micronuclei (MN) can arise from many causes, including the breakage of aberrant cytokinetic chromatin bridge. The frequent observation of MN in tumors raises the specter that they might not merely be passive elements but could instead play active roles in tumor progression. Here, we propose a mechanism that the presence of micronuclei could induce specific phenotypic and functional changes to the cell and lead to increased cancer invasive potential. Through the integration of diverse imaging and molecular techniques in vitro, supported by clinical samples from D’Amico high-risk prostate cancer (PCa) patients, our study demonstrates that the resolution of chromosome bridges can result in the accumulation of EMD and the formation of EMD-rich MN. Such structure is negative for Lamin A/C, positive for Lamin-B receptor and Sec61β. It can act as a protein sink and result in EMD pauperization from the nuclear envelope. The phenotype of emerin mis-localization is associated with molecular signature that correlates to worse prognosis in PCa and is enriched in metastatic samples. Emerin mis-localization corresponds with migratory and invasive properties of tumor cells, especially in the context collagen-rich microenvironment. Our study demonstrates that the mis-localization of emerin to MN induces increased cell invasiveness, thereby exacerbating patient’s prognosis. Biological sciences/Cell biology/Mechanisms of disease Biological sciences/Cancer/Urological cancer/Prostate cancer Biological sciences/Cell biology/Nuclear organization/Nuclear envelope Micronuclei chromatin bridge nuclear envelope emerin prostate cancer metastasis Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryMovie1.avi Supplementary Movie 1 SupplementaryMovie2.avi Supplementary Movie 2 SupplementaryMovie3.avi Supplementary Movie 3 SupplementaryMovie4.avi Supplementary Movie 4 SupplementaryMovie5.avi Supplementary Movie 5 SupplementaryMovie6.avi Supplementary Movie 6 PopedaetalSupplementaryInformationver191023.pdf Cite Share Download PDF Status: Published Journal Publication published 02 Sep, 2024 Read the published version in Experimental & Molecular Medicine → 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. 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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-3533837","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":245687106,"identity":"a84ee441-1123-4404-a413-b93d4ea8b542","order_by":0,"name":"Paulina 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invasiveness","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"experimental-and-molecular-medicine","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"emm","sideBox":"Learn more about [Experimental \u0026 Molecular Medicine](http://www.nature.com/emm/)","snPcode":"12276","submissionUrl":"https://mts-emm.nature.com/cgi-bin/main.plex","title":"Experimental \u0026 Molecular Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature 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The frequent observation of MN in tumors raises the specter that they might not merely be passive elements but could instead play active roles in tumor progression. Here, we propose a mechanism that the presence of micronuclei could induce specific phenotypic and functional changes to the cell and lead to increased cancer invasive potential. Through the integration of diverse imaging and molecular techniques in vitro, supported by clinical samples from D\u0026rsquo;Amico high-risk prostate cancer (PCa) patients, our study demonstrates that the resolution of chromosome bridges can result in the accumulation of EMD and the formation of EMD-rich MN. Such structure is negative for Lamin A/C, positive for Lamin-B receptor and Sec61β. It can act as a protein sink and result in EMD pauperization from the nuclear envelope. The phenotype of emerin mis-localization is associated with molecular signature that correlates to worse prognosis in PCa and is enriched in metastatic samples. Emerin mis-localization corresponds with migratory and invasive properties of tumor cells, especially in the context collagen-rich microenvironment. Our study demonstrates that the mis-localization of emerin to MN induces increased cell invasiveness, thereby exacerbating patient\u0026rsquo;s prognosis.\u003c/p\u003e","manuscriptTitle":"Pauperization of Emerin from nuclear envelope during chromatin bridge resolution drives prostate cancer cell migration and invasiveness","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-12 07:25:17","doi":"10.21203/rs.3.rs-3533837/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"experimental-and-molecular-medicine","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"emm","sideBox":"Learn more about [Experimental \u0026 Molecular Medicine](http://www.nature.com/emm/)","snPcode":"12276","submissionUrl":"https://mts-emm.nature.com/cgi-bin/main.plex","title":"Experimental \u0026 Molecular Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6de5009b-cc7a-4282-9d21-2322e23d5e6c","owner":[],"postedDate":"April 12th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":25944582,"name":"Biological sciences/Cell biology/Mechanisms of disease"},{"id":25944583,"name":"Biological sciences/Cancer/Urological cancer/Prostate cancer"},{"id":25944584,"name":"Biological sciences/Cell biology/Nuclear organization/Nuclear envelope"}],"tags":[],"updatedAt":"2024-09-04T17:39:52+00:00","versionOfRecord":{"articleIdentity":"rs-3533837","link":"https://doi.org/10.1038/s12276-024-01308-w","journal":{"identity":"experimental-and-molecular-medicine","isVorOnly":false,"title":"Experimental \u0026 Molecular Medicine"},"publishedOn":"2024-09-02 04:00:00","publishedOnDateReadable":"September 2nd, 2024"},"versionCreatedAt":"2024-04-12 07:25:17","video":"","vorDoi":"10.1038/s12276-024-01308-w","vorDoiUrl":"https://doi.org/10.1038/s12276-024-01308-w","workflowStages":[]},"version":"v1","identity":"rs-3533837","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3533837","identity":"rs-3533837","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}