{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T15:50:25Z","timestamp":1784562625298,"version":"3.55.0"},"reference-count":57,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,6,25]],"date-time":"2019-06-25T00:00:00Z","timestamp":1561420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The human prolyl isomerase <jats:styled-content style=\"fixed-case\">PIN<\/jats:styled-content>1, best known for its association with carcinogenesis, has recently been indicated in the disease of pancreatic ductal adenocarcinoma (PDAC). However, the functions of <jats:styled-content style=\"fixed-case\">PIN<\/jats:styled-content>1 and the feasibility of targeting <jats:styled-content style=\"fixed-case\">PIN<\/jats:styled-content>1 in <jats:styled-content style=\"fixed-case\">PDAC<\/jats:styled-content> remain elusive. For this purpose, we examined the expression of <jats:styled-content style=\"fixed-case\">PIN<\/jats:styled-content>1 in cancer, related paracarcinoma and metastatic cancer tissues by immunohistochemistry and analyzed the associations with the pathogenesis of <jats:styled-content style=\"fixed-case\">PDAC<\/jats:styled-content> in 173 patients. The functional roles of <jats:styled-content style=\"fixed-case\">PIN<\/jats:styled-content>1 in <jats:styled-content style=\"fixed-case\">PDAC<\/jats:styled-content> were explored in vitro and in vivo using both genetic and chemical <jats:styled-content style=\"fixed-case\">PIN<\/jats:styled-content>1 inhibition. We showed that <jats:styled-content style=\"fixed-case\">PIN<\/jats:styled-content>1 was upregulated in pancreatic cancer and metastatic tissues. High <jats:styled-content style=\"fixed-case\">PIN<\/jats:styled-content>1 expression is significantly association with poor clinicopathological features and shorter overall survival and disease\u2010free survival. Further stratified analysis showed that <jats:styled-content style=\"fixed-case\">PIN<\/jats:styled-content>1 phenotypes refined prognostication in <jats:styled-content style=\"fixed-case\">PDAC<\/jats:styled-content>. Inhibition of <jats:styled-content style=\"fixed-case\">PIN<\/jats:styled-content>1 expression with <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> interference or with all trans retinoic acid decreased not only the growth but also the migration and invasion of <jats:styled-content style=\"fixed-case\">PDAC<\/jats:styled-content> cells through regulating the key molecules of multiple cancer\u2010driving pathways, simultaneously resulting in cell cycle arrest and mesenchymal\u2010epithelial transition in vitro. Furthermore, genetic and chemical <jats:styled-content style=\"fixed-case\">PIN<\/jats:styled-content>1 ablation showed dramatic inhibition of the tumorigenesis and metastatic spread and then reduced the tumor burden in vivo. We provided further evidence for the use of <jats:styled-content style=\"fixed-case\">PIN<\/jats:styled-content>1 as a promising therapeutic target in <jats:styled-content style=\"fixed-case\">PDAC<\/jats:styled-content>. Genetic and chemical <jats:styled-content style=\"fixed-case\">PIN<\/jats:styled-content>1 ablation exerted potent antitumor effects through blocking multiple cancer\u2010driving pathways in <jats:styled-content style=\"fixed-case\">PDAC<\/jats:styled-content>. More potent and specific <jats:styled-content style=\"fixed-case\">PIN<\/jats:styled-content>1 targeted inhibitors could be exploited to treat this aggressive cancer.<\/jats:p>","DOI":"10.1111\/cas.14085","type":"journal-article","created":{"date-parts":[[2019,5,31]],"date-time":"2019-05-31T08:21:49Z","timestamp":1559290909000},"page":"2442-2455","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Targeting <scp>PIN<\/scp>1 exerts potent antitumor activity in pancreatic ductal carcinoma via inhibiting tumor metastasis"],"prefix":"10.1111","volume":"110","author":[{"given":"Linying","family":"Chen","sequence":"first","affiliation":[{"name":"Fujian Key Laboratory for Translational Research in Cancer and Neurodegenerative Diseases Institute for Translational Medicine The School of Basic Medical Sciences Fujian Medical University Fuzhou China"},{"name":"Department of Pathology The First Affiliated Hospital of Fujian 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Sciences Fujian Medical University Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Wang","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory for Translational Research in Cancer and Neurodegenerative Diseases Institute for Translational Medicine The School of Basic Medical Sciences Fujian Medical University Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxian","family":"Lu","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory for Translational Research in Cancer and Neurodegenerative Diseases Institute for Translational Medicine The School of Basic Medical Sciences Fujian Medical University Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingting","family":"Jiang","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory for Translational Research in Cancer and Neurodegenerative Diseases Institute for Translational Medicine The 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