AHSG confers apoptosis resistance in lung adenocarcinoma by modulating the GSK3β/β-catenin axis

AHSG confers apoptosis resistance in lung adenocarcinoma by modulating the GSK3β/β-catenin 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 Research Article AHSG confers apoptosis resistance in lung adenocarcinoma by modulating the GSK3β/β-catenin axis Moyna Kalia, Akanksha Kapoor, Deeksha Pal, Suman Dasgupta, Durba Pal This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9021786/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 9 You are reading this latest preprint version Abstract Recent studies have demonstrated that alpha-2-Heremans-Schmid glycoprotein (AHSG) is significantly upregulated in lung adenocarcinoma (LUAD), where it correlates with poor prognosis and serves as an independent prognostic factor in LUAD patients. It promotes tumor progression by enhancing cell proliferation, migration, and invasion through modulation of TGFβ/PI3K-Akt signaling and induction of epithelial-mesenchymal transition (EMT). Although the proliferative effect of AHSG is well established, its role in regulating anti-apoptotic functions and the underlying molecular mechanisms remains unexplored. In the present study, we demonstrated that elevated cytoplasmic AHSG in LUAD serves as a critical regulator of programmed cell death by targeting the GSK3β/β-catenin axis. Mechanistically, cytoplasmic AHSG interacts with GSK3β and promotes its TRAF6-mediated ubiquitination and degradation, thereby relieving β-catenin repression and facilitating its nuclear translocation. Nuclear accumulation of β-catenin in LUAD cells considerably inhibits apoptosis, thereby promoting tumor survival. Interestingly, AHSG ablation markedly inhibited the GSK3β/β-catenin pathway, leading to induction of apoptosis in LUAD cells. These findings reveal a fundamental role of AHSG in driving LUAD cancer progression and suggest that targeting AHSG may be a potential therapeutic strategy for LUAD management. Lung adenocarcinoma AHSG GSK3β glycoprotein programmed cell death Full Text Additional Declarations No competing interests reported. Supplementary Files Supplementaryfinal.pdf Supplementaryfinalapoptosis.docx Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 11 Apr, 2026 Reviews received at journal 07 Apr, 2026 Reviews received at journal 31 Mar, 2026 Reviewers agreed at journal 18 Mar, 2026 Reviewers agreed at journal 16 Mar, 2026 Reviewers invited by journal 13 Mar, 2026 Editor assigned by journal 04 Mar, 2026 Submission checks completed at journal 04 Mar, 2026 First submitted to journal 03 Mar, 2026 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-9021786","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":606326175,"identity":"64049966-4f03-4f91-80d9-42535323e3d8","order_by":0,"name":"Moyna Kalia","email":"","orcid":"","institution":"Indian Institute of Technology Ropar","correspondingAuthor":false,"prefix":"","firstName":"Moyna","middleName":"","lastName":"Kalia","suffix":""},{"id":606326176,"identity":"5c16bdc5-d928-412a-985c-0c7768db60af","order_by":1,"name":"Akanksha Kapoor","email":"","orcid":"","institution":"Indian Institute of Technology 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