title: Lipid raft-regulated IGF-1R activation antagonizes TRAIL-induced apoptosis in gastric cancer cells.
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.
authors.affiliation: Department of Medical Oncology, The First Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Qu
authors.forename: Xuejun
authors.initials: X
authors.lastname: Hu
authors.forename: Zhitu
authors.initials: Z
authors.lastname: Zhu
authors.forename: Ce
authors.initials: C
authors.lastname: Li
authors.forename: Enze
authors.initials: E
authors.lastname: Li
authors.forename: Yanju
authors.initials: Y
authors.lastname: Ma
authors.forename: Na
authors.initials: N
authors.lastname: Song
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Liu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D017209:Apoptosis; D045744:Cell Line, Tumor; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D021962:Membrane Microdomains / Q000378:metabolism*; D021381:Protein Transport; D050721:Proto-Oncogene Proteins c-cbl / Q000378:metabolism; D011719:Pyrazines / Q000494:pharmacology; D034741:RNA, Small Interfering; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: C551528:3-(8-amino-1-(2-phenylquinolin-7-yl)imidazo(1,5-a)pyrazin-3-yl)-1-methylcyclobutanol; D048868:Adaptor Proteins, Signal Transducing; D007093:Imidazoles; D011719:Pyrazines; D034741:RNA, Small Interfering; D053221:TNF-Related Apoptosis-Inducing Ligand; C492211:CBLB protein, human; D050721:Proto-Oncogene Proteins c-cbl; D017526:Receptor, IGF Type 1
keywords: Cbl-b; IGF-1R; Lipid raft; TRAIL