p65/RelA NF‐κB fragments generated by RIPK3 activity regulate tumorigenicity, cell metabolism, and stemness characteristics - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Cellular Biochemistry Année : 2022

p65/RelA NF‐κB fragments generated by RIPK3 activity regulate tumorigenicity, cell metabolism, and stemness characteristics

Martin Figeac

Résumé

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.
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Dates et versions

hal-03641788 , version 1 (29-11-2022)

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Yasmine Touil, Céline Latreche‐carton, Hassiba El Bouazzati, Anne‐lucie Nugues, Nathalie Jouy, et al.. p65/RelA NF‐κB fragments generated by RIPK3 activity regulate tumorigenicity, cell metabolism, and stemness characteristics. Journal of Cellular Biochemistry, 2022, 123 (3), pp.543-556. ⟨10.1002/jcb.30198⟩. ⟨hal-03641788⟩
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