Lipid raft‐regulated IGF‐1R activation antagonizes TRAIL‐induced apoptosis in gastric cancer cells

Gastric cancer cells are resistant to tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) and the resistance mechanism is not fully understood. In human gastric cancer MGC803 and BGC823 cells, TRAIL induces insulin‐like growth factor‐1 receptor (IGF‐1R) pathway activation. Treatment with IGF‐1R inhibitor OSI‐906 or small interfering RNAs against IGF‐1R, prevents IGF‐1R pathway activation and increases TRAIL‐induced apoptosis. The TRAIL‐induced IGF‐1R pathway activation is promoted by IGF‐1R translocation into lipid rafts. Moreover, the translocation of IGF‐1R into lipid rafts is regulated by Casitas B‐lineage lymphoma b (Cbl‐b). Taken together, TRAIL‐induced IGF‐1R activation antagonizes TRAIL‐induced apoptosis by Cbl‐b‐regulated distribution of IGF‐1R in lipid rafts.