P01.16.b Multiomics Analysis Unveils the Role of Emx2 Expression in Attenuation of Egfr Expression in Glioblastoma
Year: 2025
Type: conference-abstract
Abstract: BACKGROUND Glioblastoma (GB), the most frequent and aggressive primary brain tumor in adult, remains an incurable disease. Better knowledge of this disease is important to design novel therapies to improve patient care. The transcription factor EMX2 plays a key role during brain development. In adult, it is expressed in the neural precursors of the subventricular brain zone where it may contribute to modulating the balance between neurogenesis and astrogenesis. EMX2 has also been reported as tumor suppressor in several cancers. Eventually, EMX2 induces cell proliferation arrest in GB cells. MATERIAL AND METHODS For all experiments, we used an EMX2 doxycycline-inducible U87 cell line previously described (Monnier, 2018). In vivo tumor monitoring and survival assessment were conducted after orthotopic injection of these cells expressing luciferase into immunodeficient mice. A paired and time-resolved multiomics approach (ChIPseq, transcriptome, proteome, phosphoproteome) was performed in U87 cells expressing EMX2 or not. Integration of omics data and functional inferences were validated by RT-PCR, western blotting, immunofluorescence and immunohistochemistry. RESULTS Doxycycline-induced EMX2 expression in brain-implanted U87 cells correlated in significant tumor growth delay. The overall survival median was 71% longer in EMX2 cells implanted doxycycline-induced mice (60 days) vs cells implanted non-induced mice (35 days) with the expression of EMX2 still persistent at sacrifice in induced cells. The integration of multi-omics data unveiled an enrichment in alteration of pro-oncogenic pathways. Among those, “ERBB1 internalization pathway” belongs to one of the most frequently altered pathways in GB. We demonstrated that EMX2 expression in U87 cells correlates with a decrease in EGFR protein level and that this is due to EGFR endocytosis and lysosome degradation in a ligand independent manner. CONCLUSION We propose that expression of EMX2 modulates pro-oncogenic pathways and demonstrate a functional link between EMX2 expression and the control of EGFR signaling homeostasis in GB cells. This could be seen as a mechanism by which EMX2, a tumor suppressor gene, could exert its functions on proliferation attenuation or rather a necessity for the tumor cells to cope with EMX2 overexpression. EMX2 expression levels may thus constitute an interesting biomarker in GB that may be linked to specific vulnerabilities (e.g. EGFR signaling) to control disease progression.
Source: Neuro-Oncology
Institutions: Inserm, Oncogenesis Stress Signaling, Hôpital Pontchaillou, Centre Hospitalier Universitaire de Rennes, Université de Rennes, Centre National de la Recherche Scientifique, Institut de génétique et de développement de Rennes, Institut de génétique et de biologie moléculaire et cellulaire, Centre Eugène Marquis
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4414792255
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