p65/RelA NF-κB fragments generated by RIPK3 activity regulate tumorigenicity, cell metabolism, and stemness characteristics
| Autor: | Yasmine Touil, Céline Latreche‐Carton, Hassiba El Bouazzati, Anne‐Lucie Nugues, Nathalie Jouy, Xavier Thuru, William Laine, Frederic Lepretre, Martin Figeac, Meryem Tardivel, Jérôme Kluza, Thierry Idziorek, Bruno Quesnel |
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| Přispěvatelé: | Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Institut pour la recherche sur le cancer de Lille [Lille] (IRCL), Plateforme BioImaging Center Lille (BICeL), Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 (PLBS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur de Lille, Service des Maladies du Sang [CHU Lille] (SMS), Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Thuru, Xavier |
| Rok vydání: | 2021 |
| Předmět: |
p65/RelA
NF-kappa B Transcription Factor RelA stemness [SDV.CAN]Life Sciences [q-bio]/Cancer Apoptosis [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] Cell Biology RIPK3 fragment Biochemistry Mice [SDV.CAN] Life Sciences [q-bio]/Cancer Caspases Receptor-Interacting Protein Serine-Threonine Kinases [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] cancer Animals [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Phosphorylation Molecular Biology Melanoma ComputingMilieux_MISCELLANEOUS |
| Zdroj: | Journal of Cellular Biochemistry Journal of Cellular Biochemistry, 2022, 123 (3), pp.543-556. ⟨10.1002/jcb.30198⟩ |
| ISSN: | 1097-4644 0730-2312 |
| DOI: | 10.1002/jcb.30198⟩ |
| Popis: | International audience; Receptor-interacting protein kinase 3 (RIPK3) can induce necroptosis, apoptosis, or cell proliferation and is silenced in several hematological malignancies. We previously reported that RIPK3 activity independent of its kinase domain induces caspase-mediated p65/RelA cleavage, resulting in N-terminal 1-361 and C-terminal 362-549 fragments. We show here that a noncleavable p65/RelA D361E mutant expressed in DA1-3b leukemia cells decreases mouse survival times and that coexpression of p65/RelA fragments increases the tumorigenicity of B16F1 melanoma cells. This aggressiveness in vivo did not correlate with NF-κB activity measured in vitro. The fragments and p65/RelA D361E mutant induced different expression profiles in DA1-3b and B16F1 cells. Stemness markers were affected: p65/RelA D361E increased ALDH activity in DA1-3b cells, and fragment expression increased melanoma sphere formation in B16/F1 cells. p65/RelA fragments and the D361E noncleavable mutant decreased oxidative or glycolytic cell metabolism, with differences observed between models. Thus, p65/RelA cleavage initiated by kinase-independent RIPK3 activity in cancer cells is not neutral and induces pleiotropic effects in vitro and in vivo that may vary across tumor types. |
| Databáze: | OpenAIRE |
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