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

Jonathan Vial 1 Amélie Royet 1 Philippe Cassier 1 Antonin Tortereau 1, 2, 3 Sarah Dinvaut 1 Denis Maillet 1 Lise Gratadou-Hupon 1 Marion Creveaux 1 Alexa Sadier 4 Garance Tondeur 5 Sophie Léon 1 Lauriane Depaepe 5 Sophie Pantalacci 4 Arnaud de la Fouchardiere 6 Olivier Micheau 7 Stéphane Dalle 5 Vincent Laudet 8 Patrick Mehlen 9, * Marie Castets 1, *
* Auteur correspondant
1 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
2 ENVL - Ecole Nationale Vétérinaire de Lyon
3 ICE - Interactions Cellules Environnement - UR
4 LBMC UMR 5239 - Laboratoire de biologie et modélisation de la cellule
5 Département de Dermatologie [CH Lyon-Sud, Pierre-Bénite]
6 Centre Léon Bérard [Lyon]
7 LNC - Lipides - Nutrition - Cancer [Dijon - U1231]
8 OOB - Observatoire océanologique de Banyuls
9 CNRS - Centre National de la Recherche Scientifique
Abstract : 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.
Keywords : Ectodysplasin receptor EDAR Tumor Necrosis Factor receptor (TNFR)
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Article dans une revue
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https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01960268
Contributeur : Lnc - Université de Bourgogne <>
Soumis le : mercredi 19 décembre 2018 - 12:19:25
Dernière modification le : mercredi 10 juin 2020 - 18:42:06

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UNIV-BOURGOGNE | LNC-HSPPATHIES | CNRS | HCL | CHLS | LNC-UMR866 | UNIV-LYON1 | CRCL | SORBONNE-UNIVERSITE | ENS-LYON | SU-SCIENCES | UMS-2348 | UDL

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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, Nature Publishing Group, 2019, 26, pp.443-454. ⟨10.1038/s41418-018-0128-1⟩. ⟨hal-01960268⟩

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