Transcription Factors FOXG1 and Groucho/TLE Promote Glioblastoma Growth

Overview

Journal Nat Commun

Specialty Biology

Date 2013 Dec 21

PMID 24356439

Citations 43

Authors

Federica Verginelli

Alessandro Perin

Rola Dali

Karen H Fung

Rita Lo

Pierluigi Longatti

Marie-Christine Guiot

Rolando F Del Maestro

Sabrina Rossi

Umberto di Porzio

Owen Stechishin

Samuel Weiss

Stefano Stifani

Affiliations

Soon will be listed here.

Abstract

Glioblastoma (GBM) is the most common and deadly malignant brain cancer, with a median survival of <2 years. GBM displays a cellular complexity that includes brain tumour-initiating cells (BTICs), which are considered as potential key targets for GBM therapies. Here we show that the transcription factors FOXG1 and Groucho/TLE are expressed in poorly differentiated astroglial cells in human GBM specimens and in primary cultures of GBM-derived BTICs, where they form a complex. FOXG1 knockdown in BTICs causes downregulation of neural stem/progenitor and proliferation markers, increased replicative senescence, upregulation of astroglial differentiation genes and decreased BTIC-initiated tumour growth after intracranial transplantation into host mice. These effects are phenocopied by Groucho/TLE knockdown or dominant inhibition of the FOXG1:Groucho/TLE complex. These results provide evidence that transcriptional programmes regulated by FOXG1 and Groucho/TLE are important for BTIC-initiated brain tumour growth, implicating FOXG1 and Groucho/TLE in GBM tumourigenesis.

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