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

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• 作者：Ling Xu ; Xiujuan Qu ; Xuejun Hu ; Zhitu Zhu ; Ce Li ; Enze Li ; Yanju Ma ; Na Song ; Yunpeng Liu
• 关键词：TRAIL ; IGF-1R ; Lipid raft ; Cbl-b
• 刊名：FEBS Letters
• 出版年：29 November, 2013
• 年：2013
• 卷：587
• 期：23
• 页码：3815-3823
• 全文大小：2063 K

文摘

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.