{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:47:39Z","timestamp":1790095659901,"version":"4.0.1"},"reference-count":54,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T00:00:00Z","timestamp":1729555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T00:00:00Z","timestamp":1729555200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1U01 CA224012"],"award-info":[{"award-number":["1U01 CA224012"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54CA209988"],"award-info":[{"award-number":["U54CA209988"]}],"id":[{"id":"10.13039\/100000002","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":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The basement membrane (BM) is among the predominant microenvironmental factors of normal epithelia and of precancerous epithelial lesions. Evidence suggests that the BM functions not only as a barrier to tumour invasion but also as an active tumour\u2010suppressing signalling substrate during premalignancy. However, the molecular foundations of such mechanisms have not been elucidated. Here we explore potential tumour\u2010suppressing functions of the BM during precancer evolution, focusing on the expression and function of the extracellular matrix receptor dystroglycan in the pancreas and pancreatic disease. We show that the dystroglycan protein is highly expressed in the acinar compartment of the normal pancreas but lower in the ductal compartment. Moreover, there is a strong suppression of dystroglycan protein expression with acinar\u2010to\u2010ductal metaplasia in chronic pancreatitis and in all stages of pancreatic precancer and cancer evolution, from acinar\u2010to\u2010ductal metaplasia to dysplasia to adenocarcinoma. The conditional knockout of dystroglycan in the murine pancreas produced little evidence of developmental or functional deficiency. However, conditional deletion of dystroglycan expression in the context of oncogenic\n                    <jats:italic>Kras<\/jats:italic>\n                    expression led to a clear acceleration of pancreatic disease evolution, including accelerated dysplasia development and decreased survival. These data establish dystroglycan as a suppressor of pancreatic dysplasia development and one that is muted in chronic pancreatitis and at the earliest stages of oncogene\u2010induced transformation. We conclude that dystroglycan is an important mediator of the tumour\u2010suppressing functions of the BM during precancer evolution and that reduced dystroglycan function increases cancer risk, highlighting the dynamics of cell\u2013BM interactions as important determinants of early cancer progression. \u00a9 2024 The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.6356","type":"journal-article","created":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T05:51:30Z","timestamp":1729576290000},"page":"411-422","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Suppression of dystroglycan function accompanies pancreatic acinar\u2010to\u2010ductal metaplasia and favours dysplasia development"],"prefix":"10.1002","volume":"264","author":[{"given":"Ge","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering Oregon Health &amp; Science University  Portland OR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke","family":"Ternes","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Oregon Health &amp; Science University  Portland OR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Lanciault","sequence":"additional","affiliation":[{"name":"Providence Regional Pathology  Portland OR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"MacPherson\u2010Hawthorne","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Genetics Oregon Health &amp; Science University  Portland OR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8764-1959","authenticated-orcid":false,"given":"Young Hwan","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Oregon Health &amp; Science University  Portland OR USA"},{"name":"Knight Cancer Institute Oregon Health &amp; Science University  Portland OR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1558-2413","authenticated-orcid":false,"given":"Rosalie C","family":"Sears","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Genetics Oregon Health &amp; Science University  Portland OR USA"},{"name":"Knight Cancer Institute Oregon Health &amp; Science University  Portland OR USA"},{"name":"Brenden\u2010Colson Center for Pancreatic Care Oregon Health &amp; Science University  Portland OR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9916-5937","authenticated-orcid":false,"given":"John L","family":"Muschler","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Oregon Health &amp; Science University  Portland OR USA"},{"name":"Knight Cancer Institute Oregon Health &amp; Science University  Portland OR USA"},{"name":"Brenden\u2010Colson Center for Pancreatic Care Oregon Health &amp; Science University  Portland OR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2328"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI80007"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.12"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01322"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ctdb.2018.02.005"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201311112"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-018-0038-z"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2016.08.007"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2009.11.730"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.20411"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.432807"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.3.10.1132"},{"key":"e_1_2_8_14_1","first-page":"7102","article-title":"A role for dystroglycan in epithelial polarization: loss of function in breast tumor cells","volume":"62","author":"Muschler J","year":"2002","journal-title":"Cancer Res"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-3732"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0904515106"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-022-02812-7"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.07-8354com"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.06.003"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23548"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1053\/hupa.2001.26468"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-1638"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C900007200"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.152728"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21130"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(03)00309-X"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2005.04.023"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2011.11.010"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00907-8"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-78061-3"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-40895-6"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21261-w"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v22.i31.7046"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.061176"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00725.2010"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.070680"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/1478-811X-8-3"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2016.07.017"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e11-01-0074"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature22979"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.03103"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2011.07600.x"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.6.3.3819"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81708-0"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.145.3.619"},{"key":"e_1_2_8_47_1","first-page":"147","article-title":"Oriented basement membrane fibrils provide a memory for F\u2010actin planar polarization via the dystrophin\u2010Dystroglycan complex during tissue elongation","author":"Cerqueira Campos F","year":"2020","journal-title":"Development"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1199424"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2008.00822.x"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1454-z"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2017.11.013"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2024.149656"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5570"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2007.01.017"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.2010.00990.x"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.6356","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/path.6356","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.6356","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T23:05:47Z","timestamp":1773011147000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.6356"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,22]]},"references-count":54,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1002\/path.6356"],"URL":"https:\/\/doi.org\/10.1002\/path.6356","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,22]]},"assertion":[{"value":"2024-08-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}