Here, our data revealed that knockdown of PLOD2 resulted in decreased level of p-PI3K, p-AKT, p-GSK-3β and β-catenin, implicating that inactivated PI3K/AKT signaling may be responsible for shPLOD2-mediated suppression of glioma cell proliferation, migration and invasion. This evidence concerns the gene PLOD2 and central nervous system cancer.