GPR56/ADGRG1 inhibits mesenchymal differentiation and radioresistance in glioblastoma

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 G...

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Detalles Bibliográficos
Autores: Moreno Monasterio, Marta, Pedrosa, Leire, Paré Brunet, Laia, Pineda, Estela, Bejarano, Leire, Martínez Soler, Fina, Balasubramaniyan, Veerakumar, Ezhilarasan, Ravesanker, Kallarackal, Naveen, Kim, Sung-Hak, Wang, Jia, Audia, Alessandra, Conroy, Siobhan, Marín Aguilera, Mercedes, Ribalta Farrés, Teresa María, Pujol Farré, Teresa, Herreros, Antonio, Tortosa i Moreno, Avelina, Mira, Helena, Alonso, Marta M., Gómez-Manzano, Candelaria, Graus Ribas, Francesc, Sulman, Erik P., Piao, Xianhua, Nakano, Ichiro, Prat Aparicio, Aleix, Bhat, Krishna P., Iglesia, Núria de la
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/118923
Acceso en línea:https://hdl.handle.net/2445/118923
Access Level:acceso abierto
Palabra clave:Glioma
Tumors
Radioteràpia
Gliomas
Radiotherapy
Descripción
Sumario: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.

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