We discovered that PIK3CA mutations reprogram glutamine metabolism by up-regulating glutamate pyruvate transaminase 2 (GPT2) in colorectal cancer (CRC) cells through an AKT-independent, PDK1-ribosomal s6 kinase 2 (RSK2)-activating transcription factor 4 (ATF4) signaling axis, making them more dependent on glutamine31 (Fig. 3). This evidence concerns the gene ATF4 and colorectal carcinoma.