The invasion ability of
glioblastoma (GBM) causes
tumor cells to infiltrate the surrounding brain parenchyma and leads to poor outcomes. Transient receptor potential vanilloid 4 (TRPV4) exhibits a remarkable role in
cancer cell motility, but the contribution of TRPV4 to
glioblastoma metastasis is not fully understood. Here, we reported that TRPV4 expression was significantly elevated in
malignant glioma compared to normal brain and low-grade
glioma, and TRPV4 expression was negatively correlated with the prognosis of
glioma patients. Functionally, stimulation of TRPV4 promoted
glioblastoma cell migration and invasion, and repression of TRPV4 hindered the migration and invasion of
glioblastoma cells in vitro. Molecularly, TRPV4 strongly colocalized and interacted with skeletal
protein-
F-actin at cellular protrusions, and TRPV4 regulated the formation of invadopodia and filopodia in
glioblastoma cells. Furthermore, the Cdc42/N-wasp axis mediated the effect of TRPV4-regulated cellular protrusions and invasion. Foremost, TRPV4 inhibitor treatment or downregulation of TRPV4 significantly reduced the invasion-growth of subcutaneously and intracranially transplanted
glioblastoma in mice. In conclusion, the TRPV4/Cdc42/wasp signaling axis regulates cellular protrusion formation in
glioblastoma cells and influences the invasion-growth phenotype of
glioblastoma in vivo. TRPV4 may serve as a prognostic factor and specific therapeutic target for GBM patients.