Researchers from the Montreal Neurological Institute and Hospital at McGill University have published a study in Nature Communications that identifies two specific key players in the growth of glioblastoma (GBM).
The disease is the most common and deadly form of primary malignant brain cancer, accounting for approximately 15% of all brain tumors and occurring mostly in adults between the ages of 45 and 70. A GBM tumor contains a complex combination of different cell types including stem-like cells that are able to initiate brain tumor growth, even when present in very small numbers. These brain tumor initiating cells (BTICs) are believed to be among the cells that can re-initiate GBM if they are not completely eradicated through surgery, radiation, and chemotherapy. BTICs represent an important therapeutic target for GBM treatment strategies, according to the scientists.
“We wanted to find out how GBM-derived BTICs are able to initiate a tumor with the ultimate goal of preventing the regrowth of this deadly form of brain cancer,” said Stefano Stifani, Ph.D., a neuroscientist and senior investigator on the paper (“Transcription factors FOXG1 and Groucho/TLE promote glioblastoma growth”). “What we found is that, by impairing the activity of two transcription factors termed FOXG1 and TLE, we can significantly reduce the ability of BTICs to give rise to brain tumors.”
“These results provide evidence that transcriptional programs regulated by FOXG1 and Groucho/TLE are important for BTIC-initiated brain tumor growth, implicating FOXG1 and Groucho/TLE in GBM tumorigenesis,” wrote the investigators.
The researchers studied brain tumor growth in an in vivo mouse model using human GBM-derived BTICs. The demonstration that the FOXG1 and TLE proteins are important for the tumor-forming ability of human GBM-derived BTICs has long-term implications because FOXG1 and TLE control the expression of numerous genes. Identifying the genes whose expression is controlled by FOXG1 and TLE is expected to provide further information on the mechanisms involved in GBM tumorigenesis.
In the long term, researchers hope to identify multiple important regulators in order to find new potential therapeutic targets to impair the tumorigenic ability of BTICs.