| First Author | Vial J | Year | 2019 |
| Journal | Cell Death Differ | Volume | 26 |
| Issue | 3 | Pages | 443-454 |
| PubMed ID | 29855541 | Mgi Jnum | J:280263 |
| Mgi Id | MGI:6359007 | Doi | 10.1038/s41418-018-0128-1 |
| Citation | Vial J, et al. (2019) The Ectodysplasin receptor EDAR acts as a tumor suppressor in melanoma by conditionally inducing cell death. Cell Death Differ 26(3):443-454 |
| abstractText | 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 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. |
