| 論文名 |
Cetuximab enhances TRAIL-induced gastric cancer cell apoptosis by promoting DISC formation in lipid rafts. |
| 著者 |
Ling Xu
Xuejun Hu
Xiujuan Qu
Kezuo Hou
Huachuan Zheng
Yunpeng Liu
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| キーワード |
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| 出版年月 |
1970年1月 |
| 発表先 |
Biochem Biophys Res Commun. 2013 Sep 20;439(2):285-90. |
| WEBサイト |
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| 論文概要（和文） |
セツキシマブは脂質ラフトのDISC形成を促進することによりTRAIL誘発胃癌細胞のアポトーシスを高めます。 |
| 論文概要（英文） |
TRAIL is a member of the tumor necrosis factor family that selectively induces cancer cell apoptosis. However, gastric cancer cells are insensitive to TRAIL. Our and others studies showed that the inhibition of EGFR pathway activation could increase the sensitivity of TRAIL in cancer cells. But the detailed mechanism is not fully understood. In the present study, compared with TRAIL or cetuximab (an anti-EGFR monoclonal antibody) alone, treatment with the TRAIL/cetuximab combination significantly promoted death receptor 4 (DR4) clustering as well as the translocation of both DR4 and Fas-associated death domain-containing protein (FADD) into lipid rafts. This in turn resulted in caspase-8 cleavage and the formation of the death-inducing signaling complex (DISC) in these lipid rafts. Cholesterol-depletion with methyl-β-cyclodextrin partially prevented DR4 clustering and DISC formation, and thus partially reversed apoptosis induced by the TRAIL/cetuximab dual treatment. These results indicate that cetuximab increases TRAIL-induced gastric cancer cell apoptosis at least partially through the promotion of DISC formation in lipid rafts. |
