First, tryptophan depletion caused by the high expression of indoleamine-2,3-dioxygenase-1 (IDO1) and tryptophan-2,3-dioxygenase (TDO2) in LN229 glioblastoma cells upregulates TrpRS expression through the activation of the general control nonderepressible-2 (GCN2) kinase and phosphorylation of eukaryotic translation initiation factor 2α (eIF2α), followed by the activation of activating transcription factor 4 (ATF4). This evidence concerns the gene EIF2AK4 and glioblastoma.