{"entity": "publication", "iuid": "4a403e49a4b24b25a7832cb1f82e489d", "timestamp": "2026-09-30T22:58:50.563Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/4a403e49a4b24b25a7832cb1f82e489d.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/4a403e49a4b24b25a7832cb1f82e489d"}}, "title": "ZEB1, a novel junctional adhesion molecule A regulator, impacts sensitivity of pancreatic cancer-associated fibroblasts to reovirus.", "authors": [{"family": "Dam", "given": "Nicole", "initials": "N"}, {"family": "Harryvan", "given": "Tom J", "initials": "TJ"}, {"family": "Dang", "given": "Hao", "initials": "H"}, {"family": "Ioannidis", "given": "Gavriil", "initials": "G"}, {"family": "Schmierer", "given": "Bernhard", "initials": "B"}, {"family": "Hawinkels", "given": "Lukas J A C", "initials": "LJAC"}, {"family": "Kemp", "given": "Vera", "initials": "V"}], "type": "journal article", "published": "2025-12-18", "journal": {"title": "Mol Ther Oncol", "issn": "2950-3299", "volume": "33", "issue": "4", "pages": "201071", "issn-l": null}, "abstract": "Oncolytic virus (OV) therapy is a promising treatment for various tumors. However, in pancreatic ductal adenocarcinoma (PDAC), the high abundance of cancer-associated fibroblasts (CAFs) can limit OV therapy efficacy by impairing viral spread and anti-tumor immunity. We have previously shown that oncolytic reovirus infection of CAFs depends on the expression of the reovirus entry receptor junctional adhesion molecule A (JAM-A), which is not or lowly expressed in most PDAC CAFs. We propose that increasing JAM-A expression on CAFs will boost viral spread in a tumor. However, there are currently no known regulators of JAM-A expression. Therefore, we performed a genome-wide CRISPR-Cas9 knockout screen to identify novel regulators of JAM-A expression. Ablation of the top negative regulator, zinc finger E-box binding homeobox 1 (ZEB1), in pancreatic fibroblasts led to strong JAM-A upregulation. We show that ZEB1 directly regulates JAM-A expression by binding to the enhancer-box (E-box) regions located within the JAM-A promoter. Importantly, ZEB1 ablation increased the sensitivity of fibroblasts to reovirus infection and subsequent cell death. Our work provides a novel overview of genes regulating JAM-A expression and provides a rational approach of combining ZEB1 inhibition with reovirus therapy to target both CAFs and tumor cells in stroma-rich tumors such as PDAC.", "doi": "10.1016/j.omton.2025.201071", "pmid": "41244268", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12617759"}, {"db": "pii", "key": "S2950-3299(25)00140-7"}], "notes": [], "created": "2026-09-23T15:52:04.062Z", "modified": "2026-09-23T15:52:04.076Z"}