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This study aims to clarify its impact on the activity of cancer\u2010associated fibroblasts (CAFs), key players in PDAC progression, and patient outcomes. Early pancreatic carcinogenesis was modeled in p48\n                    <jats:sup>Cre<\/jats:sup>\n                    ; LSL\u2010Kras\n                    <jats:sup>G12D<\/jats:sup>\n                    mice with caerulein\u2010induced pancreatitis, complemented by in vitro studies on human immortalized pancreatic stellate cells (PSCs) and primary PDAC\u2010derived CAFs. Data were gained from microarray analysis, RNA sequencing (RNA\u2010seq), and single\u2010cell RNA sequencing (sc\u2010RNA\u2010seq), with subsequent bioinformatics analysis. We uncovered a specific transcriptional signature associated with fibroblast migration in early pancreatic carcinogenesis and linked it to poor survival in patients with PDAC. A pivotal role of the ARP2\/3 complex in CAF migration was identified. Inhibition of the ARP2\/3 complex markedly decreased CAF motility and induced significant morphological changes in vitro. Furthermore, its inhibition also hindered TGF\u03b21\u2010mediated myofibroblastic CAF differentiation but had no effect on IL\u20101\u2010mediated inflammatory CAF differentiation. Our findings position the ARP2\/3 complex as central to the migration and differentiation of myofibroblastic CAF. Targeting this complex presents a promising new therapeutic avenue for PDAC treatment.\n                  <\/jats:p>","DOI":"10.1002\/ijc.35246","type":"journal-article","created":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T23:39:08Z","timestamp":1730245148000},"page":"1272-1281","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["<scp>ARP2<\/scp>\n                    \/3 complex affects myofibroblast differentiation and migration in pancreatic ductal adenocarcinoma"],"prefix":"10.1002","volume":"156","author":[{"given":"Yifeng","family":"Sun","sequence":"first","affiliation":[{"name":"Department of General, Visceral and Transplantation Surgery University of Heidelberg  Heidelberg Germany"},{"name":"Beijing Tsinghua Changgung Hospital, School of Clinical Medicine Tsinghua University  Beijing China"},{"name":"Department of General and Visceral Surgery Ulm University Hospital  Ulm 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