Clinical and Translational Medicine (Jul 2022)
Identification of growth hormone receptor as a relevant target for precision medicine in low‐EGFR expressing glioblastoma
- Maïté Verreault,
- Irma Segoviano Vilchis,
- Shai Rosenberg,
- Nolwenn Lemaire,
- Charlotte Schmitt,
- Jérémy Guehennec,
- Louis Royer‐Perron,
- Jean‐Léon Thomas,
- TuKiet T. Lam,
- Florent Dingli,
- Damarys Loew,
- François Ducray,
- Sophie Paris,
- Catherine Carpentier,
- Yannick Marie,
- Florence Laigle‐Donadey,
- Audrey Rousseau,
- Natascha Pigat,
- Florence Boutillon,
- Franck Bielle,
- Karima Mokhtari,
- Stuart J. Frank,
- Aurélien deReyniès,
- Khê Hoang‐Xuan,
- Marc Sanson,
- Vincent Goffin,
- Ahmed Idbaih
Affiliations
- Maïté Verreault
- Sorbonne Université Institut du Cerveau – Paris Brain Institute – ICM, Inserm, CNRS, AP‐HP, Hôpital de la Pitié Salpêtrière Paris France
- Irma Segoviano Vilchis
- Sorbonne Université Institut du Cerveau – Paris Brain Institute – ICM, Inserm, CNRS, AP‐HP, Hôpital de la Pitié Salpêtrière Paris France
- Shai Rosenberg
- Laboratory for Cancer Computational Biology & Gaffin Center for Neuro‐Oncology Hadassah – Hebrew University Medical Center Jerusalem Israel
- Nolwenn Lemaire
- Sorbonne Université Institut du Cerveau – Paris Brain Institute – ICM, Inserm, CNRS, AP‐HP, Hôpital de la Pitié Salpêtrière Paris France
- Charlotte Schmitt
- Sorbonne Université Institut du Cerveau – Paris Brain Institute – ICM, Inserm, CNRS, AP‐HP, Hôpital de la Pitié Salpêtrière Paris France
- Jérémy Guehennec
- Sorbonne Université Institut du Cerveau – Paris Brain Institute – ICM, Inserm, CNRS, AP‐HP, Hôpital de la Pitié Salpêtrière Paris France
- Louis Royer‐Perron
- DMU Neurosciences Service de Neurologie 2‐Mazarin Sorbonne Université Institut du Cerveau – Paris Brain Institute – ICM, Inserm, CNRS, AP‐HP, Hôpital de la Pitié Salpêtrière Paris France
- Jean‐Léon Thomas
- Sorbonne Université Institut du Cerveau – Paris Brain Institute – ICM, Inserm, CNRS, AP‐HP, Hôpital de la Pitié Salpêtrière Paris France
- TuKiet T. Lam
- Mass Spectrometry & Proteomics Resource, Keck Biotechnology Resource Laboratory New Haven Connecticut USA
- Florent Dingli
- Institut Curie, Centre de Recherche, PSL Research University, Laboratoire de Spectrométrie de Masse Protéomique Paris France
- Damarys Loew
- Institut Curie, Centre de Recherche, PSL Research University, Laboratoire de Spectrométrie de Masse Protéomique Paris France
- François Ducray
- Hôpital Neurologique, Service de Neurologie B Lyon France
- Sophie Paris
- Sorbonne Université Institut du Cerveau – Paris Brain Institute – ICM, Inserm, CNRS, AP‐HP, Hôpital de la Pitié Salpêtrière Paris France
- Catherine Carpentier
- Sorbonne Université Institut du Cerveau – Paris Brain Institute – ICM, Inserm, CNRS, AP‐HP, Hôpital de la Pitié Salpêtrière Paris France
- Yannick Marie
- Sorbonne Université Institut du Cerveau – Paris Brain Institute – ICM, Inserm, CNRS, AP‐HP, Hôpital de la Pitié Salpêtrière Paris France
- Florence Laigle‐Donadey
- DMU Neurosciences Service de Neurologie 2‐Mazarin Sorbonne Université Institut du Cerveau – Paris Brain Institute – ICM, Inserm, CNRS, AP‐HP, Hôpital de la Pitié Salpêtrière Paris France
- Audrey Rousseau
- Sorbonne Université Institut du Cerveau – Paris Brain Institute – ICM, Inserm, CNRS, AP‐HP, Hôpital de la Pitié Salpêtrière Paris France
- Natascha Pigat
- Université Paris Cité INSERM UMR‐S1151, CNRS UMR‐S8253, Institut Necker Enfants Malades Paris France
- Florence Boutillon
- Université Paris Cité INSERM UMR‐S1151, CNRS UMR‐S8253, Institut Necker Enfants Malades Paris France
- Franck Bielle
- DMU Neurosciences Service de Neurologie 2‐Mazarin Sorbonne Université Institut du Cerveau – Paris Brain Institute – ICM, Inserm, CNRS, AP‐HP, Hôpital de la Pitié Salpêtrière Paris France
- Karima Mokhtari
- DMU Neurosciences Service de Neurologie 2‐Mazarin Sorbonne Université Institut du Cerveau – Paris Brain Institute – ICM, Inserm, CNRS, AP‐HP, Hôpital de la Pitié Salpêtrière Paris France
- Stuart J. Frank
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine University of Alabama Birmingham Alabama USA
- Aurélien deReyniès
- Programme Cartes d'Identité des Tumeurs (CIT) Ligue Nationale Contre le Cancer Service de Bioinformatique Paris France
- Khê Hoang‐Xuan
- DMU Neurosciences Service de Neurologie 2‐Mazarin Sorbonne Université Institut du Cerveau – Paris Brain Institute – ICM, Inserm, CNRS, AP‐HP, Hôpital de la Pitié Salpêtrière Paris France
- Marc Sanson
- DMU Neurosciences Service de Neurologie 2‐Mazarin Sorbonne Université Institut du Cerveau – Paris Brain Institute – ICM, Inserm, CNRS, AP‐HP, Hôpital de la Pitié Salpêtrière Paris France
- Vincent Goffin
- Université Paris Cité INSERM UMR‐S1151, CNRS UMR‐S8253, Institut Necker Enfants Malades Paris France
- Ahmed Idbaih
- DMU Neurosciences Service de Neurologie 2‐Mazarin Sorbonne Université Institut du Cerveau – Paris Brain Institute – ICM, Inserm, CNRS, AP‐HP, Hôpital de la Pitié Salpêtrière Paris France
- DOI
- https://doi.org/10.1002/ctm2.939
- Journal volume & issue
-
Vol. 12,
no. 7
pp. n/a – n/a
Abstract
Abstract Objective New therapeutic approaches are needed to improve the prognosis of glioblastoma (GBM) patients. Methods With the objective of identifying alternative oncogenic mechanisms to abnormally activated epidermal growth factor receptor (EGFR) signalling, one of the most common oncogenic mechanisms in GBM, we performed a comparative analysis of gene expression profiles in a series of 54 human GBM samples. We then conducted gain of function as well as genetic and pharmocological inhibition assays in GBM patient‐derived cell lines to functionnally validate our finding. Results We identified that growth hormone receptor (GHR) signalling defines a distinct molecular subset of GBMs devoid of EGFR overexpression. GHR overexpression was detected in one third of patients and was associated with low levels of suppressor of cytokine signalling 2 (SOCS2) expression due to SOCS2 promoter hypermethylation. In GBM patient‐derived cell lines, GHR signalling modulates the expression of proteins involved in cellular movement, promotes cell migration, invasion and proliferation in vitro and promotes tumourigenesis, tumour growth, and tumour invasion in vivo. GHR genetic and pharmacological inhibition reduced cell proliferation and migration in vitro. Conclusion This study pioneers a new field of investigation to improve the prognosis of GBM patients.
Keywords
- cell migration
- comparative analysis
- glioblastoma
- oncogenicity
- pre‐clinical models
- therapeutic target
