Experimental evidence indicates a critical role of TRPV4 (Transient Receptor Potential Vanilloid 4) in controlling the cell migratory activity of multiple tumors. However, the oncogenic role of TRPV4 in glioma still remains elusive. In this study, we tried to investigate the oncogenic role of TRPV4 in glioma. We found that the expression levels of TRPV4 were upregulated in glioma and the high levels of TRPV4 indicated a worse prognosis in patients with glioma. TRPV4 was critical for glioma migration and invasion: activating TRPV4 by agonist GSK1016790 A enhanced glioma migration and invasion, while, the specific TRPV4 antagonist HC-067047 suppressed glioma migration and invasion. Mechanically, activated TRPV4 promoted the activation of Rac1 (Ras-related C3 botulinum toxin substrate 1) by targeting the AKT for phosphorylation, then enhanced glioma migration and invasion. All these results suggested that TRPV4 accelerates glioma migration and invasion through the AKT/Rac1 signaling, and TRPV4 might be considered as a potential target for glioma therapy. (C) 2018 Elsevier Inc. All rights reserved.