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dc.contributor.authorFan, Kaiji
dc.contributor.authorGravemeyer, Jan
dc.contributor.authorRitter, Cathrin
dc.contributor.authorRasheed, Kashif
dc.contributor.authorGambichler, Thilo
dc.contributor.authorMoens, Ugo Lionel
dc.contributor.authorShuda, Masahiro
dc.contributor.authorSchrama, David
dc.contributor.authorBecker, Jürgen C.
dc.date.accessioned2020-03-26T07:49:46Z
dc.date.available2020-03-26T07:49:46Z
dc.date.embargoEndDate2020-07-05
dc.date.issued2019-07-07
dc.description.abstractDespite the fact that the transcription factor ATOH1 is a master regulator of Merkel cell development, its role in Merkel cell carcinoma (MCC) carcinogenesis remains controversial. Here, we provide several lines of evidence that ATOH1 is a lineage-dependent oncogene in MCC. Luciferase assays revealed binding of ATOH1 and subsequent activation to the promoter of miR-375, which is one of the most abundant microRNAs in MCCs. Overexpression of ATOH1 in variant MCC cell lines and fibroblasts induced miR-375 expression, whereas ATOH1 knockdown in classical MCC cell lines reduced miR-375 expression. Moreover, ATOH1 overexpression in these cells changed their growth characteristics from adherent to suspension and/orspheroidal growth, that is, resembling the neuroendocrine growth pattern of classical MCC cell lines. Notably, ectopic expression of different Merkel cell polyomavirus (MCPyV)-derived truncated large T antigens induced ATOH1 expression in fibroblasts, which was paralleled by miR-375 expression and similar morphologic changes. In summary, MCPyV-associated carcinogenesis is likely to induce the characteristic neuroendocrine features of MCC via induction of ATOH1; thus, ATOH1 can be regarded as a lineage-dependent oncogene in MCC.en_US
dc.identifier.citationFan, K.; Gravemeyer, J.,, Ritter, C., Rasheed, K.; Gambichler, T.; Moens,U.; Shuda, M.; Schrama, D.; Becker, J.C. (2019) MCPyV Large T antigen induced atonal homolog 1 (ATOH1) is a lineage-dependency oncogene in Merkel cell carcinoma.<i> Journal of Investigative Dermatology, 2019</i>en_US
dc.identifier.cristinIDFRIDAID 1712233
dc.identifier.doi10.1016/j.jid.2019.06.135
dc.identifier.issn0022-202X
dc.identifier.issn1523-1747
dc.identifier.urihttps://hdl.handle.net/10037/17853
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.relation.journalJournal of Investigative Dermatology
dc.rights.accessRightsembargoedAccessen_US
dc.rights.holderCopyright 2019 The Authors. Published by Elsevier, Inc. on behalf of the Society for Investigative Dermatologyen_US
dc.subjectVDP::Medical disciplines: 700en_US
dc.subjectVDP::Medisinske Fag: 700en_US
dc.titleMCPyV Large T antigen induced atonal homolog 1 (ATOH1) is a lineage-dependency oncogene in Merkel cell carcinoma.en_US
dc.type.versionacceptedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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