GPR56/ADGRG1 Inhibits Mesenchymal Differentiation and Radioresistance in Glioblastoma
Year: 2017
Type: article
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.
Source: Cell Reports
Authors: 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
Institutions: Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Hospital Clínic de Barcelona, Institut d'Investigació Biomédica de Bellvitge, Universitat de Barcelona, The University of Texas MD Anderson Cancer Center, University of Alabama at Birmingham, University Medical Center Groningen, Consejo Superior de Investigaciones Científicas, Instituto de Biomedicina de Valencia, Navarre Institute of Health Research, Centro de Investigación Médica Aplicada, Universidad de Navarra, Boston Children's Hospital, Harvard University
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,620
Funders: Fundación Ramón Areces, Generalitat de Catalunya, Ministerio de Economía y Competitividad, Universitat de Barcelona, National Institutes of Health, University of Texas MD Anderson Cancer Center, European Regional Development Fund, National Cancer Institute, National Institute of Neurological Disorders and Stroke
OpenAlex ID: W2769184795