CD44 ligation with hyaluronic acid (HA) has been shown to trigger PI3K/Rho GTPase signaling, leading to GBM invasion via regulation of actin polymerization and formation of focal adhesions.9 Accumulating evidence has indicated that cancer stem cells (CSCs),10 epithelial–mesenchymal transition (EMT) modulated by PI3K/AKT/mTOR signaling,11 proneural-mesenchymal shifts via NF-κB and JAK-STAT pathways,12 angiogenesis-invasion shifts, tumor-derived exosomes13 and miRNAs play pivotal roles in GBM migration and invasion. The gene discussed is PIK3CA; the disease is glioblastoma.