Academic Journal
Sublethal necroptosis signaling promotes inflammation and liver cancer.
| العنوان: | Sublethal necroptosis signaling promotes inflammation and liver cancer. |
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| المؤلفون: | Vucur, M., Ghallab, A., Schneider, A.T., Adili, A., Cheng, M., Castoldi, M., Singer, M.T., Büttner, V., Keysberg, L.S., Küsgens, L., Kohlhepp, M., Görg, B., Gallage, S., Barragan Avila, J.E., Unger, K., Kordes, C., Leblond, A.L., Albrecht, W., Loosen, S.H., Lohr, C., Jördens, M.S., Babler, A., Hayat, S., Schumacher, D., Koenen, M.T., Govaere, O., Boekschoten, M.V., Jors, S., Villacorta-Martin, C., Mazzaferro, V., Llovet, J.M., Weiskirchen, R., Kather, J.N., Starlinger, P., Trauner, M., Luedde, M., Heij, L.R., Neumann, U.P., Keitel, V., Bode, J.G., Schneider, R.K., Tacke, F., Levkau, B., Lammers, T., Fluegen, G., Alexandrov, T., Collins, A.L., Nelson, G., Oakley, F., Mann, D.A., Roderburg, C., Longerich, T., Weber, A., Villanueva, A., Samson, A.L., Murphy, J.M., Kramann, R., Geisler, F., Costa, I.G., Hengstler, J.G., Heikenwälder, M., Luedde, T. |
| المصدر: | Immunity 56, 1578-1595.e8 (2023) |
| بيانات النشر: | Cell Press |
| سنة النشر: | 2023 |
| المجموعة: | PuSH - Publikationsserver des Helmholtz Zentrums München |
| مصطلحات موضوعية: | Hcc, Intravital Imaging, Mlkl, Nf-κb, Rip1, Rip3, Ripk1, Ripk3, Traf2, Undead Cells |
| الوصف: | It is currently not well known how necroptosis and necroptosis responses manifest in vivo. Here, we uncovered a molecular switch facilitating reprogramming between two alternative modes of necroptosis signaling in hepatocytes, fundamentally affecting immune responses and hepatocarcinogenesis. Concomitant necrosome and NF-κB activation in hepatocytes, which physiologically express low concentrations of receptor-interacting kinase 3 (RIPK3), did not lead to immediate cell death but forced them into a prolonged “sublethal” state with leaky membranes, functioning as secretory cells that released specific chemokines including CCL20 and MCP-1. This triggered hepatic cell proliferation as well as activation of procarcinogenic monocyte-derived macrophage cell clusters, contributing to hepatocarcinogenesis. In contrast, necrosome activation in hepatocytes with inactive NF-κB-signaling caused an accelerated execution of necroptosis, limiting alarmin release, and thereby preventing inflammation and hepatocarcinogenesis. Consistently, intratumoral NF-κB-necroptosis signatures were associated with poor prognosis in human hepatocarcinogenesis. Therefore, pharmacological reprogramming between these distinct forms of necroptosis may represent a promising strategy against hepatocellular carcinoma. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/37329888; info:eu-repo/semantics/altIdentifier/wos/001051374800001; info:eu-repo/semantics/altIdentifier/isbn/1074-7613; info:eu-repo/semantics/a |
| DOI: | 10.1016/j.immuni.2023.05.017 |
| الاتاحة: | https://push-zb.helmholtz-munich.de/frontdoor.php?source_opus=68415 https://doi.org/10.1016/j.immuni.2023.05.017 |
| Rights: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.C9D93C21 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.immuni.2023.05.017 |
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