Fig. 2.

Exploring the “Go-or-Grow” dichotomy in malignant glioma. The dichotomous relationship between proliferation and invasion in GBM cells is referred to as the “Go-or-Grow” hypothesis. Genetic mutations might play a role in promoting glioma invasion; however, studies from several groups have shown that genes promoting invasion are upregulated, while proliferation genes are downregulated, in infiltrating/migrating tumor cells that are found at the peritumoral rim. Despite advances in our understanding of the cellular processes underlying glioma invasion, we know little about the molecular mechanisms that govern and regulate the switch between proliferation and invasion. Current evidence suggests that metabolic stress (hypoxia, glucose deprivation), the tumor microenvironment and the activation or suppression of key transcription factors may modulate the switch between these two distinct cellular behaviors in GBM. It is possible that therapy-resistant, invasive glioma cells (differentiated cells and GSCs) that escape surgical resection may later adopt (or revert to) a proliferative phenotype at satellite lesions, promoting rapid tumor recurrence. The blue boxes and red boxes highlight the driving forces that appear to regulate this molecular switch in differentiated glioma cells and GSCs, respectively