Collectively, our findings suggest that glutamine deprivation, through cFLIPL downregulation, facilitates TRAIL-R2/DR5-mediated NF-κB activation, which, in concert with the GCN2/ATF4 signaling pathway, drives IL-8 gene expression in human colon cancer cells. The gene discussed is EIF2AK4; the disease is malignant colon neoplasm.