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However, its mechanisms remain incompletely elucidated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>RNA sequencing was performed on primary tumor tissues and paired adjacent non-tumor tissues from PDAC patients, combined with the analysis of a GEO dataset related to PDAC liver metastasis (PDAC-LM), followed by validation using in vitro assays and mouse orthotopic liver metastasis models. Transcription factor database screening coupled with dual-luciferase reporter assays identified downstream molecules. Mass spectrometry was conducted on plasma extracellular vesicles (EVs) from PDAC patients and healthy controls, with validation by ELISA. The hepatic effects of EVs were assessed using mouse models, and in vitro EV uptake assays were performed to dissect the underlying molecular mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Transcriptomic sequencing of PDAC patients showed that elevated primary-tumor runt-related transcription factor 1 (RUNX1) expression correlates with PDAC-LM. In orthotopic murine models, RUNX1 knockdown significantly reduced liver metastasis rate from 61.54% to 8.33%. Mechanistically, RUNX1 transcriptionally upregulated integrin beta 1 (ITGB1), which was enriched in PDAC cell-secreted EVs and internalized by hepatic stellate cells (HSCs), activating the NF-\u03baB pathway to induce HSC activation and secretion of ECM proteins, inflammatory factors and chemokines. This EV-induced HSC activation thereby promoted fibrotic hepatic PMN formation and facilitated LM, as validated in murine models. Clinically, ITGB1 in plasma EVs correlated with PDAC-LM and poor prognosis, with favorable diagnostic efficacy in distinguishing PDAC-LM patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Here, we first demonstrate that ITGB1 upregulated by RUNX1 in primary PDAC cells is enriched in tumor-derived EVs and contributes to fibrotic PMN formation, thereby accelerating PDAC-LM. These pivotal findings not only unravel the intricate molecular circuitry governing PDAC-LM but also pinpoint promising biomarkers to facilitate the diagnosis and therapy of this lethal metastatic cascade.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-026-08521-3","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T11:48:24Z","timestamp":1782128904000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["RUNX1-regulated ITGB1-enriched extracellular vesicles drive pancreatic cancer liver metastasis via fibrotic pre-metastatic niche formation"],"prefix":"10.1186","volume":"24","author":[{"given":"Yi","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuilin","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuting","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaizhi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pijiang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qibin","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1155-8547","authenticated-orcid":false,"given":"Ming","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"8521_CR1","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1001\/jamaoncol.2021.6987","volume":"8","author":"JM Kocarnik","year":"2022","unstructured":"Kocarnik JM, Compton K, Dean FE, Fu W, Gaw BL, Harvey JD, et al. 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