Lipid raft-regulated IGF-1R activation antagonizes TRAIL-induced apoptosis in gastric cancer cells |
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| Authors: | Ling Xu Xiujuan Qu Xuejun Hu Zhitu Zhu Ce Li Enze Li Yanju Ma Na Song Yunpeng Liu |
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| Affiliation: | 1. Department of Medical Oncology, The First Hospital of China Medical University, Shenyang 110001, China;2. Department of Respiratory Medicine, The First Hospital of China Medical University, Shenyang 110001, China;3. Department of Medical Oncology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001, China |
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| Abstract: | 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. |
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| Keywords: | TRAIL IGF-1R Lipid raft Cbl-b |
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