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首页> 外文期刊>Cell death & disease. >Autophagy suppresses self-renewal ability and tumorigenicity of glioma-initiating cells and promotes Notch1 degradation
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Autophagy suppresses self-renewal ability and tumorigenicity of glioma-initiating cells and promotes Notch1 degradation

机译：自噬抑制了胶质瘤引发细胞的自我更新能力和致瘤性，促进了Notch1降解

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摘要

Autophagy is a vital process that involves degradation of long-lived proteins and dysfunctional organelles and contributes to cellular metabolism. Glioma-initiating cells (GICs) have the ability to self-renew, differentiate into heterogeneous types of tumor cells, and sustain tumorigenicity; thus, GICs lead to tumor recurrence. Accumulating evidence indicates that autophagy can induce stem cell differentiation and increase the lethality of temozolomide against GICs. However, the mechanism underlying the regulation of GIC self-renewal by autophagy remains uncharacterized. In the present study, autophagy induced by AZD8055 and rapamycin treatment suppressed GIC self-renewal in vitro. We found that autophagy inhibited Notch1 pathway activation. Moreover, autophagy activated Notch1 degradation, which is associated with maintenance of the self-renewal ability of GICs. Furthermore, autophagy abolished the tumorigenicity of CD133?+?U87-MG neurosphere cells in an intracranial model. These findings suggest that autophagy regulating GICs self-renewal and tumorigenicity is probably bound up with Notch1 degradation. The results of this study could aid in the design of autophagy-based clinical trials for glioma treatments, which may be of great value.
机译：自噬是一种重要的过程，涉及长期蛋白质和功能失调细胞器的降解，并有助于细胞代谢。胶质瘤引发细胞（GICS）具有自我更新的能力，分化为异质类型的肿瘤细胞，并维持致瘤性;因此，GIC导致肿瘤复发。累积证据表明自噬能诱导干细胞分化，并增加替替替莫替莫酮的杀伤性。然而，通过自噬调节GIC自我更新的机制仍然保持不协调。在本研究中，AZD8055和雷帕霉素治疗诱导的自噬抑制了GIC自我更新体外。我们发现自噬抑制了Notch1途径激活。此外，自噬激活的Notch1降级，其与维护GICS的自我更新能力相关。此外，在颅内模型中废除了CD133？+ +α+α的肿瘤性的肿瘤性。这些研究结果表明，调节术语自我更新和致瘤性的自噬可能与Notch1降解有影响。该研究的结果可以帮助设计基于自噬的胶质瘤治疗的临床试验，这可能具有很大的价值。

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