CD109 drives pro-tumorigenic cell properties in human non-small cell lung cancer through interaction with desmoglein-2

CD109 drives pro-tumorigenic cell properties in human non-small cell lung cancer through interaction with desmoglein-2 | 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 Research Article CD109 drives pro-tumorigenic cell properties in human non-small cell lung cancer through interaction with desmoglein-2 Wiebke Lückstädt, Maitreyi Rathod, Lena Möbus, Simon Bub, Ralph Lucius, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4102385/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 Cluster of differentiation 109 (CD109) is a glycosylphosphatidylinositol (GPI) anchored cell surface protein, expressed on epithelial and endothelial cells, CD4+ and CD8+ T-cells, and premature lymphocytes. CD109 interacts with different cell surface receptors and thereby modulates intracellular signaling pathways, which ultimately changes cellular functions. One well-studied example is the interaction of CD109 with the TGFβ/TGFβ-receptor complex at the cell surface. CD109 silences intracellular SMAD2/3 signaling and targets TGFβ/TGFβ-receptor to the endosomal/lysosomal compartment. In recent years, CD109 emerged as a tumor marker for different tumor entities and expression of CD109 could be linked to adverse outcome in patients. In this study, we show that silencing of CD109 in human non-small cell lung cancer (NSCLC) cells, returns these cells to an epithelial like growth phenotype. On the transcriptional level, we describe changes in cell-cell contact and epithelial-mesenchymal transition associated gene clusters. At the cell surface, we identify desmoglein-2 (DSG2) as a new interaction partner of CD109 and demonstrate CD109 dependent targeting of DSG2 to the apical cell surface, where it forms desmosomes between apical and basal cell poles. Both, CD109 and DSG2 are genetic risk factors, linked to reduced overall survival in lung adenocarcinoma patients (subtype of NSCLC). In this study, we show the expression of both proteins in the same tumor and suggest a new CD109-DSG2 axis in NSCLC patients that could present a targetable therapeutic option in the future. CD109 desmoglein-2 non-small cell lung cancer lung adenocarcinoma cell adhesion epithelial cell growth Full Text Supplementary Files 240308SupplementalMatrial.pdf 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. 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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-4102385","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":281534811,"identity":"d39cd123-803f-4484-a2b4-5e19712a4787","order_by":0,"name":"Wiebke Lückstädt","email":"","orcid":"","institution":"Kiel University: Christian-Albrechts-Universitat zu Kiel","correspondingAuthor":false,"prefix":"","firstName":"Wiebke","middleName":"","lastName":"Lückstädt","suffix":""},{"id":281534812,"identity":"0126f002-d0e9-4be3-9484-5b68c7a742bc","order_by":1,"name":"Maitreyi Rathod","email":"","orcid":"","institution":"University of Basel: 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