Fiche publication
Date publication
mai 2018
Journal
Cell death and differentiation
Auteurs
Membres identifiés du Cancéropôle Est :
Dr MICHEAU Olivier
Tous les auteurs :
Vial J, Royet A, Cassier P, Tortereau A, Dinvaut S, Maillet D, Gratadou-Hupon L, Creveaux M, Sadier A, Tondeur G, Léon S, Depaepe L, Pantalacci S, de la Fouchardière A, Micheau O, Dalle S, Laudet V, Mehlen P, Castets M
Lien Pubmed
Résumé
Ectodysplasin receptor EDAR is seen as a typical Tumor Necrosis Factor receptor (TNFR) family member known to interact with its ligand Eda-A1, and signaling mainly through the nuclear factor-kappaB (NF-κB) and c-jun N-terminal kinases pathways. Mutations in genes that encode proteins involved in EDAR transduction cascade cause anhidrotic ectodermal dysplasia. Here, we report an unexpected pro-apoptotic activity of EDAR when unbound to its ligand Eda-A1, which is independent of NF-κB pathway. Contrarily to other death receptors, EDAR does recruit caspase-8 to trigger apoptosis but solely upon ligand withdrawal, thereby behaving as the so-called dependence receptors. We propose that pro-apoptotic activity of unbound EDAR confers it a tumor suppressive activity. Along this line, we identified loss-of-pro-apoptotic function mutations in EDAR gene in human melanoma. Moreover, we show that the invalidation of EDAR in mice promotes melanoma progression in a B-Raf mutant background. Together, these data support the view that EDAR constrains melanoma progression by acting as a dependence receptor.
Référence
Cell Death Differ.. 2018 May 31;:
