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A Positive Feed-forward Loop Associating EGR1 and PDGFA Promotes Proliferation and Self-renewal in Glioblastoma Stem Cells

Fabrice Lopez 1 Philipe Paquis Fabien Almairac 2 Denys Fontaine 3 Nathalie Baeza-Kallee 4 Ellen van Obberghen-Schilling 5 Marie-Pierre Junier 6 Hervé Chneiweiss 7 Dominique Figarella-Branger 4, 8 Fanny Burel-Vandenbos 9 Jean Imbert 1 Thierry Virolle 5 Nathalie Sakakini 1 Laurent Turchi 5 Aurélie Bergon 1 Hélène Holota 10 Samah Rekim
1 TAGC - Technologies avancées pour le génôme et la clinique
2 Département de Neurochirurgie [Hôpital Pasteur de Nice]
3 CHU - Hôpital Pasteur [Nice]
4 CRO2 - Centre de Recherches en Oncologie biologique et Oncopharmacologie
5 IBV - Institut de Biologie Valrose
6 NPS - Neurosciences Paris Seine
7 NPS-04 - Plasticité gliale et neuro-oncologie = Glial Plasticity
NPS - Neurosciences Paris Seine
8 TIMONE - Hôpital de la Timone [CHU - APHM]
9 Service de pathologie
10 EDB - Evolution et Diversité Biologique
Abstract : Glioblastomas are the most common primary brain tumors, highly vascularized, infiltrating, and resistant to current therapies. This cancer leads to a fatal outcome in less than 18 months. The aggressive behavior of glioblastomas, including resistance to current treatments and tumor recurrence, has been attributed to glioma stemlike/progenitor cells. The transcription factor EGR1 (early growth response 1), a member of a zinc finger transcription factor family, has been described as tumor suppressor in gliomas when ectopically overexpressed. Although EGR1 expression in human glioblastomas has been associated with patient survival, its precise location in tumor territories as well as its contribution to glioblastoma progression remain elusive. In the present study, we show that EGR1-expressing cells are more frequent in high grade gliomas where the nuclear expression of EGR1 is restricted to proliferating/progenitor cells. We show in primary cultures of glioma stemlike cells that EGR1 contributes to stemness marker expression and proliferation by orchestrating a PDGFA-dependent growth-stimulatory loop. In addition, we demonstrate that EGR1 acts as a positive regulator of several important genes, including SHH, GLI1, GLI2, and PDGFA, previously linked to the maintenance and proliferation of glioma stemlike cells.
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Journal articles
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https://hal-amu.archives-ouvertes.fr/hal-01460121
Contributor : Lionel Spinelli <>
Submitted on : Tuesday, February 7, 2017 - 4:00:05 PM
Last modification on : Tuesday, October 13, 2020 - 3:10:10 AM

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UNIV-AMU | CNRS | UNICE | UPMC | NPS | IBPS | NPS-04 | UNIV-COTEDAZUR | INP-GLIOME | INP | SORBONNE-UNIVERSITE | UNIV-TLSE3 | SU-SCIENCES

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Fabrice Lopez, Philipe Paquis, Fabien Almairac, Denys Fontaine, Nathalie Baeza-Kallee, et al.. A Positive Feed-forward Loop Associating EGR1 and PDGFA Promotes Proliferation and Self-renewal in Glioblastoma Stem Cells. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2016, 291 (20), pp.10684-10699. ⟨10.1074/jbc.M116.720698⟩. ⟨hal-01460121⟩

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