ER stress inducer tunicamycin suppresses the self-renewal of glioma-initiating cell partly through inhibiting Sox2 translation.
ER stress inducer tunicamycin suppresses the self-renewal of glioma-initiating cell partly through inhibiting Sox2 translation.
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ER应激诱导剂衣霉素部分通过抑制Sox2翻译来抑制胶质瘤起始细胞的自我更新
DOI：
10.18632/oncotarget.8954
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发表时间：
2016-06-14
期刊：
影响因子：
--
通讯作者：
Wei Y
中科院分区：
文献类型：
--
作者：
Xing Y;Ge Y;Liu C;Zhang X;Jiang J;Wei Y
神经胶质瘤起始细胞具有肿瘤起始潜力，并且对常规化疗和放射治疗具有相对抗性。因此，它们的消除是开发有效治疗的重要因素。在这里，我们报告，内质网（ER）应激诱导剂衣霉素抑制神经胶质瘤启动细胞的自我更新所确定的神经球形成试验。此外，衣霉素降低了胶质瘤起始细胞启动肿瘤形成的效率。尽管衣霉素诱导胶质瘤起始细胞凋亡，但凋亡抑制剂z-VAD-favorites仅部分消除衣霉素诱导的胶质瘤起始细胞自我更新的减少。事实上，衣霉素在翻译水平上降低了自我更新调节因子Sox 2的表达。Sox 2的过表达明显消除了衣霉素诱导的胶质瘤起始细胞自我更新的减少。因此，衣霉素抑制胶质瘤起始细胞的自我更新和致瘤潜能部分是通过减少Sox 2的翻译。这一发现为通过控制干细胞有效治疗胶质母细胞瘤提供了线索。
Glioma-initiating cells possess tumor-initiating potential and are relatively resistant to conventional chemotherapy and irradiation. Therefore, their elimination is an essential factor for the development of efficient therapy. Here, we report that endoplasmic reticulum (ER) stress inducer tunicamycin inhibits glioma-initiating cell self-renewal as determined by neurosphere formation assay. Moreover, tunicamycin decreases the efficiency of glioma-initiating cell to initiate tumor formation. Although tunicamycin induces glioma-initiating cell apoptosis, apoptosis inhibitor z-VAD-fmk only partly abrogates the reduction in glioma-initiating cell self-renewal induced by tunicamycin. Indeed, tunicamycin reduces the expression of self-renewal regulator Sox2 at translation level. Overexpression of Sox2 obviously abrogates the reduction in glioma-initiating cell self-renewal induced by tunicamycin. Taken together, tunicamycin suppresses the self-renewal and tumorigenic potential of glioma-initiating cell partly through reducing Sox2 translation. This finding provides a cue to potential effective treatment of glioblastoma through controlling stem cells.
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DOI：
10.1158/1078-0432.ccr-09-3331
发表时间：
2010-06-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Contessa JN;Bhojani MS;Freeze HH;Ross BD;Rehemtulla A;Lawrence TS
通讯作者：
Lawrence TS
Sox2 在人胶质瘤起始细胞中被真核起始因子 4E 翻译激活
DOI：
10.1016/j.bbrc.2010.06.015
发表时间：
2010-07-09
影响因子：
3.1
作者：
Ge, Yuqing;Zhou, Fengbiao;Jiang, Jianhai
通讯作者：
Jiang, Jianhai
影响因子：
50.3
作者：
Hallahan, D;Geng, L;Clanton, J
通讯作者：
Clanton, J
影响因子：
--
作者：
Dadey DY;Kapoor V;Khudanyan A;Urano F;Kim AH;Thotala D;Hallahan DE
通讯作者：
Hallahan DE
影响因子：
4.8
作者：
Li, SN;Perlman, DM;Bitterman, PB
通讯作者：
Bitterman, PB