Elevated FOXG1 in glioblastoma stem cells cooperates with Wnt/(3-catenin to induce exit from quiescence

Glioblastoma (GBM) stem cells (GSCs) display phenotypic and molecular features reminiscent of normal neu-ral stem cells and exhibit a spectrum of cell cycle states (dormant, quiescent, proliferative). However, mech-anisms controlling the transition from quiescence to proliferation in both neural stem cells (NSCs) and GSCs are poorly understood. Elevated expression of the forebrain transcription factor FOXG1 is often observed in GBMs. Here, using small-molecule modulators and genetic perturbations, we identify a synergistic interac-tion between FOXG1 and Wnt/(3-catenin signaling. Increased FOXG1 enhances Wnt-driven transcriptional targets, enabling highly efficient cell cycle re-entry from quiescence; however, neither FOXG1 nor Wnt is essential in rapidly proliferating cells. We demonstrate that FOXG1 overexpression supports gliomagenesis in vivo and that additional (3-catenin induction drives accelerated tumor growth. These data indicate that elevated FOXG1 cooperates with Wnt signaling to support the transition from quiescence to proliferation in GSCs.

Automated summary

This study identifies a synergistic interaction between FOXG1 and Wnt/(3-catenin signaling in glioblastoma stem cells (GSCs), promoting the transition from quiescence to proliferation. The findings suggest that FOXG1 and Wnt signaling cooperate to support the cell cycle re-entry process in GSCs.