Glioblastoma cells utilize evolutionarily adapted cell metabolism to promote their malignant proliferation

Its malignancy is partly driven by the high proliferative capacity of glioblastoma cells, yet the underlying molecular mechanisms remain unclear. Recent studies have revealed transcriptomic similarities between glioblastoma cells and human fetal neural stem/progenitor cells (NSCs), suggesting that glioblastoma may exploit developmental programs that promote NSC proliferation.

Fetal human NSCs rely on glutaminolysis—a metabolic pathway induced by the human-specific mitochondrial protein ARHGAP11B—to sustain proliferation. Here, we show that ARHGAP11B expression correlates with glioma malignancy and is essential for glioblastoma cell proliferation, implicating a critical role of glutaminolysis in tumor growth. Among glutaminolysis-related enzymes, glutamic-oxaloacetic transaminase 2 (GOT2) shows a strong positive correlation with glioma grade and poor patient prognosis.