GRP78 knockdown in cells suffering from hypoxic and hypoglycemic stress induced downregulation of phosphorylated PERK and eIF2α, inactivation of ATF-4, and activation of CHOP, suggesting that GRP78 further induces apoptotic cell death in RCC cells via downregulation of the PERK/eIF2α/AFT-4 pathway under conditions of stress (Figure 5G). Here, ATF4 is linked to renal cell carcinoma.