| Autor: |
Marta Moreno, Leire Pedrosa, Laia Paré, Estela Pineda, Leire Bejarano, Josefina Martínez, Veerakumar Balasubramaniyan, Ravesanker Ezhilarasan, Naveen Kallarackal, Sung-Hak Kim, Jia Wang, Alessandra Audia, Siobhan Conroy, Mercedes Marin, Teresa Ribalta, Teresa Pujol, Antoni Herreros, Avelina Tortosa, Helena Mira, Marta M. Alonso, Candelaria Gómez-Manzano, Francesc Graus, Erik P. Sulman, Xianhua Piao, Ichiro Nakano, Aleix Prat, Krishna P. Bhat, Núria de la Iglesia |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Předmět: |
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| Zdroj: |
Cell Reports, Vol 21, Iss 8, Pp 2183-2197 (2017) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2017.10.083 |
| Popis: |
A mesenchymal transition occurs both during the natural evolution of glioblastoma (GBM) and in response to therapy. Here, we report that the adhesion G-protein-coupled receptor, GPR56/ADGRG1, inhibits GBM mesenchymal differentiation and radioresistance. GPR56 is enriched in proneural and classical GBMs and is lost during their transition toward a mesenchymal subtype. GPR56 loss of function promotes mesenchymal differentiation and radioresistance of glioma initiating cells both in vitro and in vivo. Accordingly, a low GPR56-associated signature is prognostic of a poor outcome in GBM patients even within non-G-CIMP GBMs. Mechanistically, we reveal GPR56 as an inhibitor of the nuclear factor kappa B (NF-κB) signaling pathway, thereby providing the rationale by which this receptor prevents mesenchymal differentiation and radioresistance. A pan-cancer analysis suggests that GPR56 might be an inhibitor of the mesenchymal transition across multiple tumor types beyond GBM. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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