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In this study, we performed in silico analysis of\n                    <jats:italic>WASL<\/jats:italic>\n                    expression in PDAC patients and found a correlation between low\n                    <jats:italic>WASL<\/jats:italic>\n                    expression and prolonged survival. To clarify the role of\n                    <jats:italic>Wasl<\/jats:italic>\n                    in pancreatic carcinogenesis, we used 2 oncogenic\n                    <jats:italic>Kras<\/jats:italic>\n                    \u2013based PDAC mouse models with pancreas-specific\n                    <jats:italic>Wasl<\/jats:italic>\n                    deletion. In line with human data, both mouse models had an increased survival benefit due to either impaired tumor development in the presence of the tumor suppressor\n                    <jats:italic>Trp53<\/jats:italic>\n                    or the delayed tumor progression and senescent phenotype upon genetic ablation of\n                    <jats:italic>Trp53<\/jats:italic>\n                    . Mechanistically, loss of\n                    <jats:italic>Wasl<\/jats:italic>\n                    resulted in cell-autonomous senescence through displacement of the N-WASP binding partners WASP-interacting protein (WIP) and p120ctn; vesicular accumulation of GSK3\u03b2, as well as YAP1 and phosphorylated \u03b2-catenin, which are components of the destruction complex; and upregulation of\n                    <jats:italic>Cdkn1a(p21)<\/jats:italic>\n                    , a master regulator of senescence. Our findings, thus, indicate that\n                    <jats:italic>Wasl<\/jats:italic>\n                    functions in an oncogenic manner in PDAC by promoting the deregulation of the p120-catenin\/\u03b2-catenin\/p21 pathway. Therefore, strategies to reduce N-WASP activity might improve the survival outcomes of PDAC patients.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.127275","type":"journal-article","created":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T11:01:32Z","timestamp":1589972492000},"source":"Crossref","is-referenced-by-count":7,"title":["Loss of Wasl improves pancreatic cancer outcome"],"prefix":"10.1172","volume":"5","author":[{"given":"Ana","family":"Hidalgo-Sastre","sequence":"first","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Innere Medizin II, Technical University of Munich, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judit","family":"Desztics","sequence":"additional","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Innere Medizin II, Technical University of Munich, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zahra","family":"Dantes","sequence":"additional","affiliation":[{"name":"Klinik und 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