Background/Aim: Glioblastoma (GBM) cells that adapt to the in vivo microenvironment often display enhanced invasion driven by EGFR–ERK signaling and epithelial–mesenchymal transition (EMT). This study aimed to characterize an EGFR–ERK–dependent T98G subline (T98G-xeno) and to determine how gallic acid (GA) modulates reactive oxygen species (ROS), EGFR–ERK signaling, EMT and migration. Materials and Methods: Parental T98G and T98G-xeno cells were compared for proliferation, EMT markers and migration. GA cytotoxicity, ROS, EGFR–ERK signaling and migration were assessed after GA, EGF, N-acetyl-L-cysteine (NAC) or EGFR siRNA treatment. Results: T98G-xeno cells showed faster growth, increased migration, higher levels of mesenchymal markers, and elevated basal p-EGFR/p-ERK ratio versus T98G cells. Non-apoptotic GA increased ROS, decreased p-EGFR/EGFR and p-ERK/ERK ratios, restored E-cadherin/ZO-1, reduced N-cadherin/vimentin and inhibited wound closure and migration. EGF-induced EGFR–ERK activation and migration were antagonized by GA. EGFR siRNA mimicked GA, whereas NAC attenuated GA-induced ROS and partially rescued these effects. Conclusion: GA targets a ROS–EGFR–ERK–EMT axis in T98G-xeno cells, acting as a non-cytotoxic modulator that reverses EMT and limits migration. These findings suggest that GA-based strategies may help restrain invasion in EGFR–ERK–addicted, EMT-enriched GBM.
SU et al. (Fri,) studied this question.