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Preclinical studies have shown promise for \u03b1V integrin\u2010targeted therapies; however, clinical trials have been disappointing, highlighting the need for further research. In this study, we demonstrate that integrin subunit alpha V (ITGAV) signals through both mothers against decapentaplegic homolog 4 (SMAD4)\u2010dependent or SMAD4\u2010independent pathways, depending on the genetic context. In\n                    <jats:italic>SMAD4<\/jats:italic>\n                    \u2010positive PDAC cells, ITGAV contributes to the transforming growth factor\u2010beta (TGF\u2010\u03b2) signaling pathway to regulate proliferation, migration, and invasion. Conversely, in\n                    <jats:italic>SMAD4<\/jats:italic>\n                    \u2010negative PDAC cells, ITGAV influences only proliferation and migration via activation of the mitogen\u2010activated protein kinase (MAPK)\/extracellular signal\u2010related kinase (ERK) pathway. High levels of\n                    <jats:italic>ITGAV<\/jats:italic>\n                    are also associated with poor prognostic outcomes in\n                    <jats:italic>SMAD4<\/jats:italic>\n                    wild\u2010type patients but are not prognostic in\n                    <jats:italic>SMAD4<\/jats:italic>\n                    mutant patients. Thus, ITGAV contributes to different patterns of PDAC progression. These findings suggest that stratifying PDAC patients based on both\n                    <jats:italic>SMAD4<\/jats:italic>\n                    status and\n                    <jats:italic>ITGAV<\/jats:italic>\n                    expression could inform more effective integrin\u2010targeted treatment strategies.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.70080","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T04:40:56Z","timestamp":1753936856000},"page":"3342-3359","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>ITGAV<\/scp>\n                    and\n                    <scp>SMAD4<\/scp>\n                    influence the progression and clinical outcome of pancreatic ductal adenocarcinoma"],"prefix":"10.1002","volume":"19","author":[{"given":"Daniel K. 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