{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:49:43Z","timestamp":1792043383559,"version":"4.4.0"},"reference-count":29,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Cancer cells within a single pancreatic ductal adenocarcinoma (PDAC) are most often heterogeneous in their expression of the basal or classical transcriptional program. Predominance of the basal subtype has been associated with poorer patient outcomes and increased resistance to chemotherapy. Based on this, we predicted that basal subtype would be enriched in tumors previously treated with chemotherapy, and in metastases derived from primary PDAC tumors with a mixed basal\/classical population. To create matched classical and basal cell lines, we stably transduced two classical PDAC cell lines (AsPC1 and HPAFII) with the basal program transcriptional driver \u2206Np63\u03b1 or an mCherry control and assessed their growth, metastasis, and response to chemotherapy both in\u00a0vitro and in\u00a0vivo. Forced expression of \u2206Np63\u03b1 successfully converted both cell lines to basal transcriptomic subtype, yet the basal program failed to drive increased cell growth or chemoresistance in culture and did not affect tumor growth of AsPC1 in the murine pancreas. In mice orthotopically engrafted with \u2206Np63\u03b1\u2010expressing cells, no statistically significant increase in spontaneous pulmonary metastases was observed for AsPC1 or HPAFII, however, pulmonary metastases were enriched for \u2206Np63 expression as compared to established primary tumors, including expression of endogenous \u2206Np63 in the mCherry control. Increased resistance to irinotecan chemotherapy was observed in \u2206Np63\u03b1\u2009+\u2009HPAFII, yet treatment selected for \u2206Np63\u2010negative cells in both HPAFII and ASPC1. In summary, our data show that PDAC metastases are enriched for basal subtype, but chemotherapy treatment does not preferentially select for basal\u2010type cells.<\/jats:p>","DOI":"10.1002\/cam4.72322","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:39:38Z","timestamp":1792042778000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Basal Marker\n                    <scp>\u0394Np63\u03b1<\/scp>\n                    Is Enriched in Pancreatic Cancer Metastases but Not in Primary Tumors Post\u2010Chemotherapy"],"prefix":"10.1002","volume":"15","author":[{"given":"Daniel H.","family":"Ryan","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Biology, Center for Cancer Research National Cancer Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9171-4724","authenticated-orcid":false,"given":"Yuuki","family":"Ohara","sequence":"additional","affiliation":[{"name":"Laboratory of Human Carcinogenesis, Center for Cancer Research National Cancer Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3976-6233","authenticated-orcid":false,"given":"Michael J.","family":"Kruhlak","sequence":"additional","affiliation":[{"name":"Laboratory of Cancer Biology and Genetics, Center for Cancer Research National Cancer Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Center for Cancer Research National Cancer Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0868-4069","authenticated-orcid":false,"given":"Miao","family":"Lin","sequence":"additional","affiliation":[{"name":"Dartmouth Cancer Center and Dartmouth Health  Lebanon New Hampshire USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4766-0535","authenticated-orcid":false,"given":"Chin\u2010Hsien","family":"Tai","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Center for Cancer Research National Cancer Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1661-0957","authenticated-orcid":false,"given":"Christine","family":"Alewine","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Center for Cancer Research National Cancer Institute, National Institutes of Health  Bethesda Maryland USA"},{"name":"Dartmouth Cancer Center and Dartmouth Health  Lebanon New Hampshire USA"},{"name":"Department of Medicine Geisel School of Medicine at Dartmouth  Lebanon New Hampshire USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,14]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21871"},{"key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1038\/ng.3398","article-title":"Virtual Microdissection Identifies Distinct Tumor\u2010 and Stroma\u2010Specific Subtypes of Pancreatic Ductal Adenocarcinoma","volume":"47","author":"Moffitt R. 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