Molecular mechanisms of RACK1-driven metastasis in pancreatic ductal adenocarcinoma revealed by single-cell RNA sequencing

Molecular mechanisms of RACK1-driven metastasis in pancreatic ductal adenocarcinoma revealed by single-cell RNA sequencing | 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 Molecular mechanisms of RACK1-driven metastasis in pancreatic ductal adenocarcinoma revealed by single-cell RNA sequencing Hangyu Liu, Tingxin Wang, Yuying Cui, Biao Zhang, Dong Shang, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7002928/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with significant cellular heterogeneity, which poses a major challenge for treatment. We integrated three single-cell RNA sequencing (scRNA-seq) datasets to construct an expression matrix, identify cell types, and assess copy number variation (CNV) scores, with a particular focus on ductal cells. Our study found that ductal cells are the primary source of malignant cells in PDAC and identified a high-malignancy subtype—ductal cell-3—where RACK1 was the most significantly differentially expressed gene. Through the analysis of public and clinical data, along with RT-qPCR and immunohistochemistry validation, we confirmed the high expression of RACK1 in PDAC tumors, which correlated with lymph node metastasis, clinical staging, histological differentiation, and prognosis. Further investigation revealed that RACK1 promotes PDAC cell proliferation, migration, and invasion. Sequencing analysis indicated that RACK1 inhibits the FOXO signaling pathway, promotes epithelial-mesenchymal transition (EMT), and facilitates the progression and metastasis of PDAC. This study provides new insights into the role of RACK1 in PDAC and its underlying mechanisms. Pancreatic ductal adenocarcinoma scRNA-seq RACK1 RNA-seq EMT Full Text Additional Declarations No competing interests reported. Supplementary Files supplementarymaterials.zip Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 28 Jul, 2025 Reviews received at journal 27 Jul, 2025 Reviews received at journal 19 Jul, 2025 Reviews received at journal 18 Jul, 2025 Reviewers agreed at journal 15 Jul, 2025 Reviewers agreed at journal 14 Jul, 2025 Reviewers agreed at journal 14 Jul, 2025 Reviewers invited by journal 14 Jul, 2025 Editor assigned by journal 01 Jul, 2025 Submission checks completed at journal 01 Jul, 2025 First submitted to journal 29 Jun, 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. 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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-7002928","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":485492855,"identity":"ccced8fc-94f4-40ef-95cd-695a9b4b3b1f","order_by":0,"name":"Hangyu Liu","email":"","orcid":"","institution":"First Affiliated Hospital of Dalian Medical University","correspondingAuthor":false,"prefix":"","firstName":"Hangyu","middleName":"","lastName":"Liu","suffix":""},{"id":485492856,"identity":"630f6ab8-575f-4e3c-9092-b6851160e436","order_by":1,"name":"Tingxin Wang","email":"","orcid":"","institution":"First Affiliated Hospital of Dalian Medical 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