Recently, Winnay et al. observed that inhibition of the PI3K/AKT pathway results in reduced phosphorylation of PERK at Thr-980, leading to a reduction in expression of ATF4 and CHOP as well as a decrease in phosphorylated IRE1, BIP, and XBP1s in tunicamycin-treated brown preadipocytes, hepa1c1c7 mouse hepatoma cells, and mouse embryonic fibroblasts, suggesting a positive role of this pathway in induction of ERS [52]. This evidence concerns the gene ATF4 and hepatocellular carcinoma.