In this manuscript we demonstrate that RIOK1 and RIOK2 become overexpressed in GBM tumor cells relative to normal brain cells; that RIOK1 and RIOK2 overexpression occurs in response to constitutive Akt signaling; that RIOK2 forms a complex with RIOK1, mTor, and other signaling components to drive activation of Akt signaling and tumorigenesis; and that, in GBM cells, RIOK1 or RIOK2 loss causes a reduction in Akt signaling and provokes p53-dependent apoptosis, cell cycle exit, and chemosensitivity through the RpL11-dependent ribosomal stress checkpoint. This evidence concerns the gene RIOK2 and neoplasm.