Targeting OGG1 arrests cancer cell proliferation by inducing replication stress
| العنوان: | Targeting OGG1 arrests cancer cell proliferation by inducing replication stress |
|---|---|
| المؤلفون: | Visnes, T., Benítez-Buelga, C., Cázares-Körner, A., Sanjiv, K., Hanna, B.M.F., Mortusewicz, O., Rajagopal, V., Albers, J.J., Hagey, D.W., Bekkhus, T., Eshtad, S., Baquero, J.M., Masuyer, G., Wallner, O., Müller, S., Pham, T., Göktürk, C., Rasti, A., Suman, S., Torres-Ruiz, R., Sarno, A., Wiita, E., Homan, E.J., Karsten, S., Marimuthu, K., Michel, M., Koolmeister, T., Scobie, M., Loseva, O., Almlöf, I., Unterlass, J.E., Pettke, A., Boström, J., Pandey, M., Gad, H., Herr, P., Jemth, A.-S., El Andaloussi, S., Kalderén, C., Rodriguez-Perales, S., Benítez, J., Krokan, H.E., Altun, M., Stenmark, P., Berglund, U.W., Helleday, T. |
| المصدر: | 12234-12251 Nucleic Acids Research |
| بيانات النشر: | Oxford Academic, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | DNA Replication, Guanine, DNA Repair, AcademicSubjects/SCI00010, Poly (ADP-Ribose) Polymerase-1, Mice, Nude, Antineoplastic Agents, Genome Integrity, Repair and Replication, DNA Glycosylases, Mice, Cell Line, Tumor, repair and replication, Animals, Humans, Molecular Targeted Therapy, Enzyme Inhibitors, RNA, Small Interfering, Cell Proliferation, DNA, Neoplasm, HCT116 Cells, Survival Analysis, Xenograft Model Antitumor Assays, Genome integrity, Tumor Burden, Gene Expression Regulation, Neoplastic, Oxidative Stress, Colonic Neoplasms, Reactive Oxygen Species, DNA Damage, Signal Transduction |
| الوصف: | Altered oncogene expression in cancer cells causes loss of redox homeostasis resulting in oxidative DNA damage, e.g. 8-oxoguanine (8-oxoG), repaired by base excision repair (BER). PARP1 coordinates BER and relies on the upstream 8-oxoguanine-DNA glycosylase (OGG1) to recognise and excise 8-oxoG. Here we hypothesize that OGG1 may represent an attractive target to exploit reactive oxygen species (ROS) elevation in cancer. Although OGG1 depletion is well tolerated in non-transformed cells, we report here that OGG1 depletion obstructs A3 T-cell lymphoblastic acute leukemia growth in vitro and in vivo, validating OGG1 as a potential anti-cancer target. In line with this hypothesis, we show that OGG1 inhibitors (OGG1i) target a wide range of cancer cells, with a favourable therapeutic index compared to non-transformed cells. Mechanistically, OGG1i and shRNA depletion cause S-phase DNA damage, replication stress and proliferation arrest or cell death, representing a novel mechanistic approach to target cancer. This study adds OGG1 to the list of BER factors, e.g. PARP1, as potential targets for cancer treatment. C The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0305-1048 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::7fd8ce19837332df7926ecb7122c0d29 https://hdl.handle.net/11250/2788132 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.pmid.dedup....7fd8ce19837332df7926ecb7122c0d29 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 03051048 |
|---|