Post transcriptional control restrains the IL17–GCSF axis and limits neutrophil-driven breast cancer metastasis

Post transcriptional control restrains the IL17–GCSF axis and limits neutrophil-driven breast cancer metastasis | 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 Post transcriptional control restrains the IL17–GCSF axis and limits neutrophil-driven breast cancer metastasis Raúl Méndez, Alba Millanes Romero, Belén Guillén Tirado, Judit Martín, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7545087/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 Inflammatory cues remodel the tumor secretome, yet how stress coupled translational control in the tumor niche programs this intercellular communication remains unclear. Although translational control has been studied mainly as a cell autonomous driver of tumor growth, chronic inflammation, hypoxia and nutrient limitation impose endoplasmic reticulum (ER) stress that can rewire translation of secreted factors and thereby tumor–immune crosstalk. Here we show that Cytoplasmic polyadenylation element‐binding protein 4 (CPEB4) integrates pro-inflammatory environmental stress cues into mRNA stabilization in tumor cells establishing a negative feedback branch of IL 17 signaling. Ribosome profiling and RIP seq define two IL 17 regulated mRNA classes: a feedback limiting module that is bound by and requires CPEB4 for cytoplasmic polyadenylation, stability and translation, and a CPEB4 independent branch exemplified by Csf3. Loss of CPEB4 collapses the former while leaving the latter hyperactive, uncoupling post transcriptional restraint from transcriptionally linked outputs. This shift elevates tumor derived G CSF, drives systemic neutrophilia and accelerates pre metastatic niche maturation and lung metastasis in a breast cancer model. Our data establish CPEB4 as a post transcriptional rheostat that shapes tumor–immune crosstalk and suggest a novel strategy for targeting the IL 17–G CSF axis for metastasis prone breast cancer. Biological sciences/Cell biology/Mechanisms of disease Health sciences/Oncology/Cancer/Breast cancer Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryInformation.MillanesRomeroetal.pdf Supplementary Information 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-7545087","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":518717527,"identity":"b80e14e6-e9df-4e5a-8e5d-4284ea822fbd","order_by":0,"name":"Raúl 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