David Diaz-Carballo, Sahitya Saka, Ali Haydar Acikelli, Ekaterina Homp, Julia Erwes, Rebecca Demmig, Jacqueline Klein, Katrin Schröer, Sascha Malak, Flevy D’Souza, Adrien Noa-Bolaño, Saskia Menze, Emilio Pano, Swetlana Andrioff, Marc Teipel, Philip Dammann, Diana Klein, Amber Nasreen, Andrea Tannapfel, Nicole Grandi, Enzo Tramontano, Crista Ochsenfarth, Dirk Strumberg
- In this work, we are reporting that "Shock and Kill", a therapeutic approach designed to eliminate latent HIV from cell reservoirs, is extrapolatable to cancer therapy. This is based on the observation that malignant cells express a spectrum of human endogenous retroviral elements (HERVs) which can be transcriptionally boosted by HDAC inhibitors. The endoretroviral gene \(\it HERV-V2\) codes for an envelope protein, which resembles syncytins. It is significantly overexpressed upon exposure to HDAC inhibitors and can be effectively targeted by simultaneous application of TLR7/8 agonists, triggering intrinsic apoptosis. We demonstrated that this synergistic cytotoxic effect was accompanied by the functional disruption of the TLR7/8-NF\(\kappa\)B, Akt/PKB, and Ras-MEK-ERK signalling pathways. CRISPR/Cas9 ablation of \(\it TLR7\) and \(\it HERV-V1/V2\) curtailed apoptosis significantly, proving the pivotal role of these elements in driving cell death. The effectiveness of this new approach was confirmed in ovarian tumour xenograft studies, revealing a promising avenue for future cancer therapies.
MetadatenAuthor: | David Diaz-CarballoGND, Sahitya SakaORCiDGND, Ali Haydar AcikelliORCiDGND, Ekaterina HompGND, Julia ErwesGND, Rebecca DemmigGND, Jacqueline KleinORCiDGND, Katrin SchröerORCiDGND, Sascha MalakGND, Flevy D’SouzaGND, Adrien Noa-BolañoORCiDGND, Saskia MenzeGND, Emilio PanoORCiDGND, Swetlana AndrioffORCiDGND, Marc TeipelGND, Philip DammannGND, Diana KleinORCiDGND, Amber NasreenGND, Andrea TannapfelORCiDGND, Nicole GrandiGND, Enzo TramontanoGND, Crista OchsenfarthORCiDGND, Dirk StrumbergGND |
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URN: | urn:nbn:de:hbz:294-97162 |
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DOI: | https://doi.org/10.1038/s42003-021-01800-3 |
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Parent Title (English): | Communications biology |
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Publisher: | Springer Nature |
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Place of publication: | London |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2023/03/02 |
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Date of first Publication: | 2021/03/03 |
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Publishing Institution: | Ruhr-Universität Bochum, Universitätsbibliothek |
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Volume: | 4 |
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Issue: | Article 276 |
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First Page: | 276-1 |
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Last Page: | 276-16 |
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Note: | Dieser Beitrag ist auf Grund des DEAL-Springer-Vertrages frei zugänglich. |
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Institutes/Facilities: | Marienhospital Herne, Medizinische Klinik III, Hämatologie / Onkologie |
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Dewey Decimal Classification: | Technik, Medizin, angewandte Wissenschaften / Medizin, Gesundheit |
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open_access (DINI-Set): | open_access |
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faculties: | Medizinische Fakultät |
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Licence (English): | Creative Commons - CC BY 4.0 - Attribution 4.0 International |
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