| Literature DB >> 29166609 |
Marta Moreno1, Leire Pedrosa2, Laia Paré3, Estela Pineda4, Leire Bejarano1, Josefina Martínez5, Veerakumar Balasubramaniyan6, Ravesanker Ezhilarasan7, Naveen Kallarackal7, Sung-Hak Kim8, Jia Wang8, Alessandra Audia9, Siobhan Conroy10, Mercedes Marin3, Teresa Ribalta11, Teresa Pujol12, Antoni Herreros13, Avelina Tortosa5, Helena Mira14, Marta M Alonso15, Candelaria Gómez-Manzano6, Francesc Graus16, Erik P Sulman7, Xianhua Piao17, Ichiro Nakano8, Aleix Prat18, Krishna P Bhat9, Núria de la Iglesia19.
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.Entities:
Keywords: GPR56; NF-κB; glioblastoma; glioma stem-like initiating cell; mesenchymal differentiation; radioresistance; tumor plasticity
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Year: 2017 PMID： 29166609 DOI： 10.1016/j.celrep.2017.10.083
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423