The Ectodysplasin receptor EDAR acts as a tumor suppressor in melanoma by conditionally inducing cell death - Université de Bourgogne Accéder directement au contenu
Article Dans Une Revue Cell Death and Differentiation Année : 2019

The Ectodysplasin receptor EDAR acts as a tumor suppressor in melanoma by conditionally inducing cell death

Denis Maillet
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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.

Dates et versions

hal-01960268 , version 1 (19-12-2018)

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Citer

Jonathan Vial, Amélie Royet, Philippe Cassier, Antonin Tortereau, Sarah Dinvaut, et al.. The Ectodysplasin receptor EDAR acts as a tumor suppressor in melanoma by conditionally inducing cell death. Cell Death and Differentiation, 2019, 26, pp.443-454. ⟨10.1038/s41418-018-0128-1⟩. ⟨hal-01960268⟩
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