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Oxaliplatin enhances TRAIL-induced apoptosis in gastric cancer cells by CBL-regulated death receptor redistribution in lipid rafts |
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| Authors: | Ling Xu Xiujuan Qu Ye Zhang Xianghong Yang Yuee Teng Kiyonao Sada |
| Institution: | a Department of Medical Oncology, The First Hospital of China Medical University, No. 155, North Nanjing Street, Shenyang 110001, China b Department of Respiratory Medicine, The First Hospital of China Medical University, Shenyang 110001, China c Department of Pathology, The Shengjing Hospital of China Medical University, Shenyang 110004, China d Division of Microbiology, Department of Pathological Sciences, School of Medicine, University of Fukui, Fukui 9101193, Japan |
| Abstract: | Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor family that selectively induces apoptosis in cancer cells. However, gastric cancer cells are insensitive to TRAIL. In the present study, we show that oxaliplatin enhanced TRAIL-induced apoptosis of MGC803, BGC823, and SGC7901 cells. Oxaliplatin promoted death receptor 4 (DR4) and death receptor 5 (DR5) clustering into aggregated lipid rafts, while the cholesterol-sequestering agent nystatin partially prevented lipid raft aggregation, DR4 and DR5 clustering, and reduced apoptosis. Furthermore, the expression of the casitas B-lineage lymphoma (Cbl) family was downregulated by oxaliplatin. Transfection of c-Cbl or Cbl-b partially reversed oxaliplatin-induced lipid raft aggregation. These results indicated that oxaliplatin enhanced TRAIL-induced gastric cancer cell apoptosis at least partially through Cbl-regulated death receptor redistribution in lipid rafts. |
| Keywords: | TRAIL tumor necrosis factor-related apoptosis-inducing ligand Cbl casitas B-lineage lymphoma TNF tumor necrosis factor DR4 death receptor 4 DR5 death receptor 5 DISC death-inducing signaling complex |
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