{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T05:20:50Z","timestamp":1778044850071,"version":"3.51.4"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,10,23]],"date-time":"2019-10-23T00:00:00Z","timestamp":1571788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008903","name":"Ministry of Health and Welfare","doi-asserted-by":"publisher","award":["MOHW108\u2010TDU\u2010B\u2010212\u2010124020"],"award-info":[{"award-number":["MOHW108\u2010TDU\u2010B\u2010212\u2010124020"]}],"id":[{"id":"10.13039\/100008903","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003711","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST 102\u20102628\u2010B\u2010400\u2010MY3"],"award-info":[{"award-number":["MOST 102\u20102628\u2010B\u2010400\u2010MY3"]}],"id":[{"id":"10.13039\/501100003711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003711","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["104\u20102314\u2010B\u2010400\u2010022 MOST"],"award-info":[{"award-number":["104\u20102314\u2010B\u2010400\u2010022 MOST"]}],"id":[{"id":"10.13039\/501100003711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004700","name":"Taipei Medical University","doi-asserted-by":"publisher","award":["DP2\u2010107\u201021121\u2010C\u201004"],"award-info":[{"award-number":["DP2\u2010107\u201021121\u2010C\u201004"]}],"id":[{"id":"10.13039\/501100004700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and treatment\u2010resistant malignancy. The lack of pathway\u2010informed biomarkers hampers the development of rational diagnostics or therapies. Recently, the protein abnormal spindle\u2010like microcephaly\u2010associated (ASPM) was identified as a novel Wnt and stemness regulator in PDAC, while the pathogenic roles of its protein isoforms remain unclarified. We developed novel isoform\u2010specific antibodies and genetic knockdown (KD) of putative ASPM isoforms, whereby we uncovered that the levels of ASPM isoform 1 (iI) and ASPM\u2010iII are variably upregulated in PDAC cells. ASPM isoforms show remarkably different subcellular locations; specifically, ASPM\u2010iI is exclusively localized to the cortical cytoplasm of PDAC cells, while ASPM\u2010iII is predominantly expressed in cell nuclei. Mechanistically, ASPM\u2010iI co\u2010localizes with disheveled\u20102 and active \u03b2\u2010catenin as well as the stemness marker aldehyde dehydrogenase\u20101 (ALDH\u20101), and its expression is indispensable for the Wnt activity, stemness, and the tumorigenicity of PDAC cells. By contrast, ASPM\u2010iII selectively regulates the expression level of cyclin E and cell cycle progression in PDAC cells. The expression of ASPM\u2010iI and ASPM\u2010iII displays considerable intratumoral heterogeneity in PDAC tissues and only that of ASPM\u2010iI was prognostically significant; it outperformed ALDH\u20101 staining and clinico\u2010pathological variables in a multivariant analysis. Collectively, the distinct expression patterns and biological functions of ASPM isoforms may illuminate novel molecular mechanisms and prognosticators in PDAC and may pave the way for the development of therapies targeting this novel oncoprotein. \u00a9 2019 The Authors.\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.5341","type":"journal-article","created":{"date-parts":[[2019,8,29]],"date-time":"2019-08-29T11:53:47Z","timestamp":1567079627000},"page":"498-508","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["The differential distributions of ASPM isoforms and their roles in Wnt signaling, cell cycle progression, and pancreatic cancer prognosis"],"prefix":"10.1002","volume":"249","author":[{"given":"Chung\u2010Chi","family":"Hsu","sequence":"first","affiliation":[{"name":"Laboratory of Advanced Molecular Therapeutics Wan Fang Hospital, Taipei Medical University  Taipei Taiwan"},{"name":"Graduate Institute of Clinical Medicine College of Medicine, Taipei Medical University  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen\u2010Ying","family":"Liao","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine College of Medicine, Taipei Medical University  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tze\u2010Sian","family":"Chan","sequence":"additional","affiliation":[{"name":"Laboratory of Advanced Molecular Therapeutics Wan Fang Hospital, Taipei Medical University  Taipei Taiwan"},{"name":"Integrative Therapy Center for Gastroenterologic Cancers Wan Fang Hospital, Taipei Medical University  Taipei 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