Oxaliplatin enhances TRAIL-induced apoptosis in gastric cancer cells by CBL-regulated death receptor redistribution in lipid rafts

Xu, Ling; Qu, Xiujuan; Zhang, Ye; Hu, Xuejun; Yang, Xianghong; Hou, Kezuo; Teng, Yuee; Zhang, Jingdong; Sada, Kiyonao; Liu, Yunpeng

doi:10.1016/j.febslet.2009.02.014

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Volume 583, Issue 5 , Pages 943-948, 4 March 2009

Oxaliplatin enhances TRAIL-induced apoptosis in gastric cancer cells by CBL-regulated death receptor redistribution in lipid rafts

Edited by Lukas Huber

Ling Xu
- Department of Medical Oncology, The First Hospital of China Medical University, No. 155, North Nanjing Street, Shenyang 110001, China
- Ling Xu and Xiujuan Qu contributed equally to this work.
Xiujuan Qu
- Department of Medical Oncology, The First Hospital of China Medical University, No. 155, North Nanjing Street, Shenyang 110001, China
- Ling Xu and Xiujuan Qu contributed equally to this work.
Ye Zhang
- Department of Medical Oncology, The First Hospital of China Medical University, No. 155, North Nanjing Street, Shenyang 110001, China
Xuejun Hu
- Department of Respiratory Medicine, The First Hospital of China Medical University, Shenyang 110001, China
Xianghong Yang
- Department of Pathology, The Shengjing Hospital of China Medical University, Shenyang 110004, China
Kezuo Hou
- Department of Medical Oncology, The First Hospital of China Medical University, No. 155, North Nanjing Street, Shenyang 110001, China
Yuee Teng
- Department of Medical Oncology, The First Hospital of China Medical University, No. 155, North Nanjing Street, Shenyang 110001, China
Jingdong Zhang
- Department of Medical Oncology, The First Hospital of China Medical University, No. 155, North Nanjing Street, Shenyang 110001, China
Kiyonao Sada
- Division of Microbiology, Department of Pathological Sciences, School of Medicine, University of Fukui, Fukui 9101193, Japan
Yunpeng Liu
- Department of Medical Oncology, The First Hospital of China Medical University, No. 155, North Nanjing Street, Shenyang 110001, China
- Corresponding author. Fax: +86 24 83282543.

Received 11 December 2008; received in revised form 10 February 2009; accepted 10 February 2009. published online 19 February 2009.

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.

Abbreviations: 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