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 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.
Original language | English |
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Pages (from-to) | 2183-2197 |
Number of pages | 15 |
Journal | Cell reports |
Volume | 21 |
Issue number | 8 |
DOIs | |
Publication status | Published - 21-Nov-2017 |
Keywords
- PROTEIN-COUPLED RECEPTOR
- INTEGRATED GENOMIC ANALYSIS
- NF-KAPPA-B
- BREAST-CANCER
- RADIATION RESPONSE
- GENE-EXPRESSION
- STEM-CELLS
- MALIGNANT GLIOMA
- GROWTH-FACTOR
- RNA-SEQ