Publicaciones científicas

GPR56/ADGRG1 Inhibits Mesenchymal Differentiation and Radioresistance in Glioblastoma

21-nov-2017 | Revista: Cell Reports

Marta Moreno  1 , Leire Pedrosa  2 , Laia Paré  3 , Estela Pineda  4 , Leire Bejarano  1 , Josefina Martínez  5 , Veerakumar Balasubramaniyan  6 , Ravesanker Ezhilarasan  7 , Naveen Kallarackal  7 , Sung-Hak Kim  8 , Jia Wang  8 , Alessandra Audia  9 , Siobhan Conroy  10 , Mercedes Marin  3 , Teresa Ribalta  11 , Teresa Pujol  12 , Antoni Herreros  13 , Avelina Tortosa  5 , Helena Mira  14 , Marta M Alonso  15 , Candelaria Gómez-Manzano  6 , Francesc Graus  16 , Erik P Sulman  7 , Xianhua Piao  17 , Ichiro Nakano  8 , Aleix Prat  18 , Krishna P Bhat  9 , Núria de la Iglesia  19


Abstract

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.

CITA DEL ARTÍCULO  Cell Rep. 2017 Nov 21;21(8):2183-2197. doi: 10.1016/j.celrep.2017.10.083