Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Fan, K; Gravemeyer, J; Ritter, C; Rasheed, K; Gambichler, T; Moens, U; Shuda, M; Schrama, D; Becker, JC.
MCPyV Large T Antigen-Induced Atonal Homolog 1 Is a Lineage-Dependency Oncogene in Merkel Cell Carcinoma.
J Invest Dermatol. 2020; 140(1):56-65
Doi: 10.1016/j.jid.2019.06.135
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- Führende Autor*innen der Med Uni Graz
- Becker Jürgen Christian
- Fan Kaiji
- Co-Autor*innen der Med Uni Graz
- Ritter Cathrin
- Schrama David
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- Abstract:
- Despite 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. Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Antigens, Viral, Tumor - genetics
- Antigens, Viral, Tumor - metabolism
- Basic Helix-Loop-Helix Transcription Factors - genetics
- Carcinogenesis -
- Carcinoma, Merkel Cell - genetics
- Cell Differentiation -
- Cell Line, Tumor -
- Cell Lineage -
- Gene Expression Regulation, Neoplastic -
- Humans -
- Merkel cell polyomavirus - physiology
- MicroRNAs - genetics
- Oncogenes - genetics
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- Skin Neoplasms - genetics
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