{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T21:43:01Z","timestamp":1776202981553,"version":"3.50.1"},"reference-count":16,"publisher":"Portland Press Ltd.","issue":"03","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,2,12]]},"abstract":"<jats:p>Malignant progression of pancreatic ductal adenocarcinoma (PDAC) is driven by transforming growth factor (TGF)-\u03b21 through extensive cross-talk with other signalling pathways. Prompted by the observation that the ubiquitous protein programmed cell death 10 (PDCD10) is more abundantly expressed in PDAC tumour tissue compared with normal pancreas and highly correlated with reduced patient survival, authors examined its function as a modulator of TGF-\u03b2 signalling in PDAC. Cytotoxicity assays with PDAC-derived tumour cell lines, PaTu8902 (DPC4+\/+) and PaTu8988t (DPC4-\/-) engineered to homozygously lack PDCD10 showed that PDCD10 renders cells more chemoresistant to anticancer drugs. Moreover, PDCD10 promoted TGF-\u03b21-dependent proliferation by inactivating the retinoblastoma 1 protein (pRb) via a SMAD4-dependent pathway, and TGF-\u03b21-driven EMT by increasing ERK1\/2 activation via a non-SMAD4 pathway. Phosphorylation of pRB and ERK by PDCD10 is facilitated by binding of PDCD10 to MST4. Targeting PDCD10 in PDAC patients may represent a promising new strategy to improve TGF-\u03b2 targeted therapies<\/jats:p>","DOI":"10.1042\/cs20241916","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T14:32:21Z","timestamp":1739370741000},"page":"281-286","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["PDCD10\/CCM3, a potential target for pancreatic ductal adenocarcinoma?"],"prefix":"10.1042","volume":"139","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7552-2087","authenticated-orcid":false,"given":"Hendrik","family":"Ungefroren","sequence":"first","affiliation":[{"name":"First Department of Medicine, University Hospital Schleswig-Holstein (UKSH), and University of L\u00fcbeck, Ratzeburger Allee 160, 23538 L\u00fcbeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2025,2,4]]},"reference":[{"key":"2025021308274381300_CS-2024-1916C1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/s41392-020-00436-9","article-title":"Targeting TGF\u03b2 signal transduction for cancer therapy","volume":"6","author":"Liu","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"2025021308274381300_CS-2024-1916C2","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1042\/CS20240450","article-title":"PDCD10 promotes the tumor-supporting functions of TGF-\u03b2 in pancreatic cancer","volume":"138","author":"Zhou","year":"2024","journal-title":"Clin. Sci."},{"key":"2025021308274381300_CS-2024-1916C3","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/nature12207","article-title":"EndMT contributes to the onset and progression of cerebral cavernous malformations","volume":"498","author":"Maddaluno","year":"2013","journal-title":"Nature New Biol."},{"key":"2025021308274381300_CS-2024-1916C4","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s10020-020-00157-3","article-title":"Down-regulated miR-495 can target programmed cell death 10 in ankylosing spondylitis","volume":"26","author":"Ni","year":"2020","journal-title":"Mol. Med."},{"key":"2025021308274381300_CS-2024-1916C5","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1016\/j.gendis.2020.12.008","article-title":"The multifaceted PDCD10\/CCM3 gene","volume":"8","author":"Valentino","year":"2021","journal-title":"Genes Dis."},{"key":"2025021308274381300_CS-2024-1916C6","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2023.1230382","article-title":"Molecular profiling and specific targeting of gemcitabine-resistant subclones in heterogeneous pancreatic cancer cell populations","volume":"13","author":"F\u00e4rber","year":"2023","journal-title":"Front. Oncol."},{"key":"2025021308274381300_CS-2024-1916C7","doi-asserted-by":"crossref","first-page":"5532","DOI":"10.3390\/cancers13215532","article-title":"Epithelial to Mesenchymal Transition: Key Regulator of Pancreatic Ductal Adenocarcinoma Progression and Chemoresistance","volume":"13","author":"Palamaris","year":"2021","journal-title":"Cancers (Basel)"},{"key":"2025021308274381300_CS-2024-1916C8","first-page":"S44","article-title":"TGF-beta signaling in cancer--a double-edged sword","volume":"11","author":"Akhurst","year":"2001","journal-title":"Trends Cell Biol."},{"key":"2025021308274381300_CS-2024-1916C9","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.3390\/cancers13061357","article-title":"Autocrine TGF\u03b21 opposes exogenous TGF\u03b21-induced cell migration and growth arrest through sustainment of a feed-forward loop involving MEK-ERK signaling","volume":"13","author":"Ungefroren","year":"2021","journal-title":"Cancers (Basel)"},{"key":"2025021308274381300_CS-2024-1916C10","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41392-024-02099-2","article-title":"Dynamic allostery: a novel mechanism regulating autocrine and paracrine TGF-\u03b2 signalling","volume":"10","author":"Ungefroren","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"2025021308274381300_CS-2024-1916C11","doi-asserted-by":"crossref","first-page":"3791","DOI":"10.3390\/cancers15153791","article-title":"TAp73 Inhibits EMT and cell migration in pancreatic cancer cells through promoting SMAD4 expression and SMAD4-dependent inhibition of ERK activation","volume":"15","author":"Ungefroren","year":"2023","journal-title":"Cancers (Basel)"},{"key":"2025021308274381300_CS-2024-1916C12","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.1093\/annonc\/mdr617","article-title":"Contribution of CXCR4 and SMAD4 in predicting disease progression pattern and benefit from adjuvant chemotherapy in resected pancreatic adenocarcinoma","volume":"23","author":"Bachet","year":"2012","journal-title":"Ann. Oncol"},{"key":"2025021308274381300_CS-2024-1916C13","doi-asserted-by":"crossref","first-page":"6519","DOI":"10.1158\/1078-0432.CCR-12-0827","article-title":"Genetically defined subsets of human pancreatic cancer show unique in vitro chemosensitivity","volume":"18","author":"Cui","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"2025021308274381300_CS-2024-1916C14","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.3390\/cells13171442","article-title":"PDCD10 is a key player in TMZ-resistance and tumor cell regrowth: insights into its underlying mechanism in glioblastoma cells","volume":"13","author":"Zhu","year":"2024","journal-title":"Cells"},{"key":"2025021308274381300_CS-2024-1916C15","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.biopha.2018.02.020","article-title":"Dual function of programmed cell death 10 (PDCD10) in drug resistance","volume":"101","author":"Urfali-Mamatoglu","year":"2018","journal-title":"Biomed. Pharmacother"},{"key":"2025021308274381300_CS-2024-1916C16","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1038\/s41419-021-04139-z","article-title":"Programmed cell death 10 promotes metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma via PP2Ac-mediated YAP activation","volume":"12","author":"Sun","year":"2021","journal-title":"Cell Death Dis."}],"container-title":["Clinical Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/139\/03\/281\/968030\/cs-2024-1916.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/139\/03\/281\/968030\/cs-2024-1916.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T08:27:56Z","timestamp":1739435276000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/clinsci\/article\/139\/03\/281\/235642\/PDCD10-CCM3-a-potential-target-for-pancreatic"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2]]},"references-count":16,"journal-issue":{"issue":"03","published-print":{"date-parts":[[2025,2,12]]}},"URL":"https:\/\/doi.org\/10.1042\/cs20241916","relation":{},"ISSN":["0143-5221","1470-8736"],"issn-type":[{"value":"0143-5221","type":"print"},{"value":"1470-8736","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,2]]},"published":{"date-parts":[[2025,2]]}}}