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

https://doi.org/10.1074/jbc.M116.720698Get rights and content
Under a Creative Commons license
open access

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.

cancer biology
cancer stem cells
cell proliferation
cell signaling
transcription factor

Cited by (0)

*

This work was supported by grants from the Association Sauvons Laura, Agence Nationale pour la Recherche (ANR Jeunes Chercheurs, Jeunes Chercheuses, “GLIOMIRSTEM project” and ANR-10-INBS-0009-10), Fondation de France, Association pour la Recherche sur le Cancer ARC Project SFI20111203773, INCA PLBIO2012, INSERM, UNSA, and ITMO CANCER PLAN CANCER Epigenetic. The authors declare that they have no conflicts of interest with the contents of this article.

This article contains supplemental Tables S1 and S2 and Figs. S1 and S2.

1

These authors contributed equally to this work.