4EGI-1 induces apoptosis and enhances radiotherapy sensitivity in nasopharyngeal carcinoma cells via DR5 induction on 4E-BP1 dephosphorylation.
4EGI-1 induces apoptosis and enhances radiotherapy sensitivity in nasopharyngeal carcinoma cells via DR5 induction on 4E-BP1 dephosphorylation.
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4EGI-1通过DR5诱导4E-BP1去磷酸化诱导鼻咽癌细胞凋亡并增强放疗敏感性
DOI：
10.18632/oncotarget.7824
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发表时间：
2016-04-19
期刊：
影响因子：
--
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Wang W;Li J;Wen Q;Luo J;Chu S;Chen L;Qing Z;Xie G;Xu L;Alnemah MM;Li M;Fan S;Zhang H
由不同的eIF 4 E结合蛋白（4 E-BPs）调控的eIF 4F复合物可以启动蛋白质的合成。小分子化合物4 EGI-1是一种通过干扰eIF 4 E和eIF 4G（eIF 4 E复合物的主要成分）之间的相互作用而抑制帽依赖性翻译起始的抑制剂，已报道在许多类型的癌症中通过诱导细胞凋亡来抑制细胞增殖。死亡受体5（DR 5）是外源性凋亡途径中的主要成分。但目前尚未发现鼻咽癌中4 EGI-1、DR 5和4 E-BPs之间的相关性。因此，本研究拟探讨4 EGI-1在鼻咽癌细胞凋亡过程中的作用，以及4 EGI-1、DR 5和4 E-BPs之间的关系。我们的研究结果显示DR 5在鼻咽癌组织中的表达显著下调，且与淋巴结转移状态和临床分期呈负相关。DR 5表达降低是鼻咽癌预后不良的独立生物标志物，DR 5表达升高则显示174例鼻咽癌患者的总生存时间延长。此外，4 EGI-1通过4 E-BP 1上的DR 5-caspase-8轴诱导鼻咽癌细胞凋亡，eIF 4 E去磷酸化对其抗肿瘤活性有积极影响。DR 5的诱导也使鼻咽癌细胞对放疗敏感，SER为1.195。这些结果确立了死亡受体途径作为eIF 4 E/eIF 4G相互作用抑制剂在NPC中的一种新的抗癌机制。
The eIF4F complex regulated by a various group of eIF4E-binding proteins (4E-BPs) can initial the protein synthesis. Small molecule compound 4EGI-1, an inhibitor of the cap-dependent translation initiation through disturbing the interaction between eIF4E and eIF4G which are main elements of the eIF4E complex, has been reported to suppress cell proliferation by inducing apoptosis in many types of cancer. And death receptor 5 (DR5) is a major component in the extrinsic apoptotic pathway. However, the correlation among 4EGI-1, DR5 and 4E-BPs have not been discovered in NPC now. Therefore, we intend to find out the effect of 4EGI-1 on the apoptosis process of NPC and the relationship among 4EGI-1, DR5 and 4E-BPs. Our results revealed a significant down regulation of DR5 expression in NPC tissues, which inversely correlated with lymph node metastasis status and clinical stages. Depressed DR5 expression was an independent biomarker for poor prognosis in NPC, and elevated DR5 expression showed longer overall survival time in 174 NPC patients. Besides, 4EGI-1 induced apoptosis in NPC cells through the DR5-caspase-8 axis on 4E-BP1 and eIF4E dephosphorylation exerting positive influence on their anti-tumor activities. The induction of DR5 also sensitized NPC cells to radiotherapy, and the SER was 1.195. These results establish the death receptor pathway as a novel anticancer mechanism of eIF4E/eIF4G interaction inhibitor in NPC.
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影响因子：
8.8
作者：
Descamps, G.;Gomez-Bougie, P.;Tamburini, J.;Green, A.;Bouscary, D.;Maiga, S.;Moreau, P.;Le Gouill, S.;Pellat-Deceunynck, C.;Amiot, M.
通讯作者：
Amiot, M.
影响因子：
64.8
作者：
Richter, JD;Sonenberg, N
通讯作者：
Sonenberg, N
影响因子：
4.1
作者：
Paku, Keum Soon;Umenaga, Yu;Tomoo, Koji
通讯作者：
Tomoo, Koji
影响因子：
5.7
作者：
Cheung, Arthur Kwok Leung;Ip, Joseph Chok Yan;Lung, Maria Li
通讯作者：
Lung, Maria Li
影响因子：
11.4
作者：
Nelson, MR;Leidal, AM;Smibert, CA
通讯作者：
Smibert, CA