LRIG1 regulates the balance between proliferation and quiescence in glioblastoma stem cells

Glioblastoma (GBM) patients have a poor prognosis due to glioblastoma stem cells (GSCs) that resist current treatments. Leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins, particularly Lrig1, play a role in growth factor signaling in various stem cells. In this study, the function of Lrig1 in glioblastoma stem cells was investigated using gain- and loss-of-function experiments. Removing Lrig1 in cultured GBM stem cells increased proliferation and reduced quiescence, while overexpression of Lrig1 enhanced quiescence and reduced proliferation. Mice transplanted with Lrig1-deficient GBM stem cells had lower survival rates and tumors with more proliferative cells and fewer quiescent cells. The deficiency in BMP signaling responses in Lrig1-null cells may explain their lack of responsiveness to quiescence cues. These findings highlight the importance of Lrig1 in controlling responsiveness to growth factor signaling and the balance between quiescent and proliferative subpopulations in GBMs.