Regulation of the Integrated Stress Response through ATF4 and FAM129A in Prostate Cancer

Cancer cells exploit many of the cellular adaptive responses to support their survival needs. One such critical pathway in eukaryotic cells is the integrated stress response (ISR) that is important in normal physiology as well as disease states, including cancer. Since ISR can serve as a lever between survival and death, regulated control of its activity is critical for tumor formation and growth although the underlying mechanisms are poorly understood. Here we show that the main transcriptional effector of ISR, activating transcription factor 4 (ATF4), is essential for prostate cancer (PCa) growth and survival. LNCaP cells were transfected with control siRNA or an ATF4-specific siRNA, and 4 days later treated with 300nM Tg for 5h. Total RNA was isolated and Illumina Human HT-12 expression Bead-Chips (Illumina) were used for global transcriptome analysis according to the manufacturer’s protocol. The experiment was performed in triplicates. LNCaP cells were induced with Thapsigargin treated with either scrambled siRNA as control or ATF4- specific siRNA. 3 replicates per group.