Lipid raft-regulated IGF-1R activation antagonizes TRAIL-induced apoptosis in gastric cancer cells
Lipid raft-regulated IGF-1R activation antagonizes TRAIL-induced apoptosis in gastric cancer cells
复制标题
脂筏调节的 IGF-1R 激活拮抗 TRAIL 诱导的胃癌细胞凋亡
DOI：
10.1016/j.febslet.2013.10.007
复制
发表时间：
2013-11-29
期刊：
影响因子：
3.5
通讯作者：
Liu, Yunpeng
中科院分区：
文献类型：
--
作者：
Xu, Ling;Qu, Xiujuan;Liu, Yunpeng
胃癌细胞对肿瘤坏死因子相关凋亡诱导配体（TRAIL）具有耐药性，且耐药机制尚不完全清楚。在人胃癌 MGC803 和 BGC823 细胞中，TRAIL 诱导胰岛素样生长因子-1 受体 (IGF-1R) 通路激活。使用 IGF-1R 抑制剂 OSI-906 或针对 IGF-1R 的小干扰 RNA 进行治疗，可防止 IGF-1R 通路激活并增加 TRAIL 诱导的细胞凋亡。 IGF-1R 易位至脂筏中可促进 TRAIL 诱导的 IGF-1R 通路激活。此外，IGF-1R 易位至脂筏中受到 Casitas B 系淋巴瘤 b (Cbl-b) 的调节。总之，TRAIL 诱导的 IGF-1R 激活通过 Cbl-b 调节 IGF-1R 在脂筏中的分布来拮抗 TRAIL 诱导的细胞凋亡。 (C) 2013 年欧洲生化学会联合会。由 Elsevier B.V 出版。保留所有权利。
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. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.