We also found that (a) PLOD3 is differentially expressed during tumor progression, (b) PLOD3 expression promotes apoptosis in lung cancer by activating caspase-2,4-dependent signaling through ER stress-induced IRE1α activation and caspase-3-dependent apoptosis, and (c) PLOD3 siRNA, combined with chemotherapeutic drugs, can increase cancer cell death, suggesting that PLOD3 is a potential therapeutic target in cancer. The gene discussed is ERN1; the disease is lung carcinoma.