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You are here: Home / Teams / Comparative and Integrative Genomics of Organ Development - S.Pantalacci/M. Semon / Publications / The Ectodysplasin receptor EDAR acts as a tumor suppressor in melanoma by conditionally inducing cell death.

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

Jonathan Vial, Amelie Royet, Philippe Cassier, Antonin Tortereau, Sarah Dinvaut, Denis Maillet, Lise Gratadou-Hupon, Marion Creveaux, Alexa Sadier, Garance Tondeur, Sophie Leon, Lauriane Depaepe, Sophie Pantalacci, Arnaud de la Fouchardiere, Olivier Micheau, Stephane Dalle, Vincent Laudet, Patrick Mehlen, and Marie Castets (2018)

Cell Death Differ.

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-kappaB) 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-kappaB pathway. Contrarily to other death receptors, EDAR doesrecruit 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 promotesmelanoma progression in a B-Raf mutant background. Together, these data support the view that EDAR constrains melanoma progression by acting as a dependence receptor.

 
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