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ARTÍCULO

GPR56/ADGRG1 inhibits mesenchymal differentiation and radioresistance in glioblastoma

Autores: Moreno, M.; Pedrosa, L.; Pare, L. ; Pineda, E.; Bejarano, L.; Martinez, J.; Balasubramaniyan, V. ; Ezhilarasan, R.; Kallarackal, N.; Kim, S. H.; Wang, J.; Audia, A. ; Conroy, S.; Marin, M.; Ribalta, T.; Pujol, T.; Herreros, A.; Tortosa, A.; Mira, H.; Alonso Roldán, Marta María; Gomez-Manzano, C.; Graus, F.; Sulman, E. P. ; Piao, X. H.; Nakano, I. ; Prat, A.; Bhat, K. P.; de la Iglesia, N.
Título de la revista: CELL REPORTS
ISSN: 2211-1247
Volumen: 21
Número: 8
Páginas: 2183 - 2197
Fecha de publicación: 2017
Resumen:
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 classicalGBMs 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-kappa B) 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.
DOI: https://doi.org/10.1016/j.celrep.2017.10.083
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