Trop-2 governs anti-metastatic desmosomal integrity

Trop-2 governs anti-metastatic desmosomal integrity | 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 Trop-2 governs anti-metastatic desmosomal integrity Ondřej Vacek, Jiřina Procházková, Tomasz Witold Radaszkiewicz, and 28 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6123457/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 10 You are reading this latest preprint version Abstract Epithelial integrity prevents cancer cell dissemination into distant organs. While the desmosomes, formed by desmosomal proteins such as desmogleins, are critical for epithelial cohesion, their regulation in cancer remains poorly understood. Here, we show that desmogleins (DSG) directly interact with Trophoblast cell surface antigen 2 (Trop-2), a cell adhesion molecule with paradoxical roles in tumor biology. Loss of Trop 2 disrupts this partnership, impairing desmosome formation and intercellular adhesion. Mechanistically, this destabilization drives breast cancer metastasis in vivo through increased matrix metalloproteinase 14 (MMP14, MT1-MMP) production, a key regulator of extracellular matrix degradation and invasion. Our findings show that the Trop-2–DSG2 axis preserves epithelial integrity and suppresses tumor progression, clarifying the function of desmosomes in metastasis. Biological sciences/Cancer/Metastasis Biological sciences/Cancer/Breast cancer Trop-2 desmosomes epithelial integrity breast cancer metastasis Full Text Additional Declarations (Not answered) Supplementary Files Supplementaryfile2Gatingstrategy.pdf Supplementary file 2 Supplementaryfile4tophitsRNAseqtumors.pdf Supplementary file 4 Supplementaryfile3tophitsminiTurboIDMSanalysis.pdf Supplementary file 3 Supplementaryfile6tophitsproteomics.pdf Supplementary file 6 Supplementaryfile7tophitsproteomicscells.pdf Supplementary file 7 Supplementaryfile1Uncroppedmembranes.pdf Supplementary file 1 Supplementarytables15antibodies.docx Supplementary tables 1-5 Supplementaryfile5tophitsRNAseqcells.pdf Supplementary file 5 Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: revise 21 May, 2025 Review # 1 received at journal 16 May, 2025 Review # 2 received at journal 08 May, 2025 Reviewer # 2 agreed at journal 03 May, 2025 Reviewer # 1 agreed at journal 02 May, 2025 Reviewers invited by journal 02 May, 2025 Submission checks completed at journal 25 Apr, 2025 First submitted to journal 24 Apr, 2025 Unknown event 24 Apr, 2025 Editor assigned by journal 23 Apr, 2025 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-6123457","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":459755304,"identity":"e9fa3767-d422-4d4d-95b2-e995a35234f2","order_by":0,"name":"Ondřej Vacek","email":"","orcid":"https://orcid.org/0000-0002-5199-8689","institution":"Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 612 00 Brno, Czech Republic; International Clinical Research Center, St. Anne's University Hospital in Brno, 602 00 Brno, Czech Republic; Department of Experimental Biology, Faculty of Science, Masaryk 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1-5","description":"","filename":"Supplementarytables15antibodies.docx","url":"https://assets-eu.researchsquare.com/files/rs-6123457/v1/bcf9509110d2a1f84b049146.docx"},{"id":86924241,"identity":"c3285724-cff6-43b1-82f4-aa60e637a6f1","added_by":"auto","created_at":"2025-07-17 08:16:49","extension":"pdf","order_by":8,"title":"","display":"","copyAsset":false,"role":"supplement","size":358656,"visible":true,"origin":"","legend":"Supplementary file 5","description":"","filename":"Supplementaryfile5tophitsRNAseqcells.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6123457/v1/02941e2cbef382c6fef470b3.pdf"}],"financialInterests":"(Not answered)","formattedTitle":"Trop-2 governs anti-metastatic desmosomal integrity","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"cell-death-and-disease","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"cddis","sideBox":"Learn more about [Cell Death \u0026 Disease](http://www.nature.com/cddis/)","snPcode":"41419","submissionUrl":"https://mts-cddis.nature.com/cgi-bin/main.plex","title":"Cell Death \u0026 Disease","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Trop-2, desmosomes, epithelial integrity, breast cancer, metastasis","lastPublishedDoi":"10.21203/rs.3.rs-6123457/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6123457/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Epithelial integrity prevents cancer cell dissemination into distant organs. While the desmosomes, formed by desmosomal proteins such as desmogleins, are critical for epithelial cohesion, their regulation in cancer remains poorly understood. Here, we show that desmogleins (DSG) directly interact with Trophoblast cell surface antigen 2 (Trop-2), a cell adhesion molecule with paradoxical roles in tumor biology. Loss of Trop 2 disrupts this partnership, impairing desmosome formation and intercellular adhesion. Mechanistically, this destabilization drives breast cancer metastasis in vivo through increased matrix metalloproteinase 14 (MMP14, MT1-MMP) production, a key regulator of extracellular matrix degradation and invasion. Our findings show that the Trop-2–DSG2 axis preserves epithelial integrity and suppresses tumor progression, clarifying the function of desmosomes in metastasis.","manuscriptTitle":"Trop-2 governs anti-metastatic desmosomal integrity","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-17 08:16:44","doi":"10.21203/rs.3.rs-6123457/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2025-05-21T08:21:01+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2025-05-16T13:22:27+00:00","index":1,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2025-05-09T02:05:42+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-05-03T13:43:36+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-05-02T12:13:45+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2025-05-02T12:10:40+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-25T13:32:31+00:00","index":"","fulltext":""},{"type":"submitted","content":"Cell Death \u0026 Disease","date":"2025-04-24T13:31:06+00:00","index":"","fulltext":""},{"type":"checksFailed","content":"","date":"2025-04-24T13:21:55+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-23T09:20:50+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"cell-death-and-disease","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"cddis","sideBox":"Learn more about [Cell Death \u0026 Disease](http://www.nature.com/cddis/)","snPcode":"41419","submissionUrl":"https://mts-cddis.nature.com/cgi-bin/main.plex","title":"Cell Death \u0026 Disease","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b2cb7fa4-5bcc-4dc9-a6e6-9e17ab15f868","owner":[],"postedDate":"July 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[{"id":48837565,"name":"Biological sciences/Cancer/Metastasis"},{"id":48837566,"name":"Biological sciences/Cancer/Breast cancer"}],"tags":[],"updatedAt":"2025-07-17T08:16:44+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-17 08:16:44","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6123457","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6123457","identity":"rs-6123457","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}