We have recently found that mutant PIK3CA licensed TRAIL and CD95L to induce an amoeboid morphology in CRC cells, which is associated with increased invasiveness in vitro.9 Here, we show that targeting of the aberrantly active PI3K/Akt signaling pathway in TRAIL resistant, PIK3CA-mutated CRC cells only partially restored death receptor-triggered apoptosis induction. This evidence concerns the gene AKT1 and colorectal carcinoma.