{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:48:17Z","timestamp":1786978097981,"version":"build-2736575974"},"reference-count":39,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T00:00:00Z","timestamp":1720656000000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Merkel cell carcinoma (MCC) is a highly aggressive skin cancer associated with integration of Merkel cell polyomavirus (MCPyV). MCPyV\u2010encoded T\u2010antigens (TAs) are pivotal for sustaining MCC's oncogenic phenotype, i.e., repression of TAs results in reactivation of the RB pathway and subsequent cell cycle arrest. However, the MCC cell line LoKe, characterized by a homozygous loss of the RB1 gene, exhibits uninterrupted cell cycle progression after shRNA\u2010mediated TA repression. This unique feature allows an in\u2010depth analysis of the effects of TAs beyond inhibition of the RB pathway, revealing the decrease in expression of stem cell\u2010related genes upon panTA\u2010knockdown. Analysis of gene regulatory networks identified members of the E2F family (E2F1, E2F8, TFDP1) as key transcriptional regulators that maintain stem cell properties in TA\u2010expressing MCC cells. Furthermore, minichromosome maintenance (\n                    <jats:italic>MCM<\/jats:italic>\n                    ) genes, which encodes DNA\u2010binding licensing proteins essential for stem cell maintenance, were suppressed upon panTA\u2010knockdown. The decline in stemness occurred simultaneously with neural differentiation, marked by the increased expression of neurogenesis\u2010related genes such as neurexins, BTG2, and MYT1L. This upregulation can be attributed to heightened activity of PBX1 and BPTF, crucial regulators of neurogenesis pathways. The observations in LoKe were confirmed in an additional MCPyV\u2010positive MCC cell line in which RB1 was silenced before panTA\u2010knockdown. Moreover, spatially resolved transcriptomics demonstrated reduced TA expression in situ in a part of a MCC tumor characterized by neural differentiation. In summary, TAs are critical for maintaining stemness of MCC cells and suppressing neural differentiation, irrespective of their impact on the RB\u2010signaling pathway.\n                  <\/jats:p>","DOI":"10.1002\/jmv.29789","type":"journal-article","created":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T03:14:35Z","timestamp":1720667675000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Merkel cell polyomavirus pan\u2010T antigen knockdown reduces cancer cell stemness and promotes neural differentiation independent of RB1"],"prefix":"10.1002","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6804-8914","authenticated-orcid":false,"given":"Kuan Cheok","family":"Lei","sequence":"first","affiliation":[{"name":"German Cancer Research Centre (DKFZ) Heidelberg Germany"},{"name":"Translational Skin Cancer Research German Cancer Consortium (DKTK) Heidelberg 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