Laboratory of Nervous System Disorders and Therapy, GIGA-Neurosciences Research Centre, University of Liège, 4000 Liège, Belgium.
Department of Neurosurgery, CHU of Liège, 4000 Liège, Belgium.
Cells. 2019 Nov 29;8(12):1542. doi: 10.3390/cells8121542.
Cancer cells are continually exposed to environmental stressors forcing them to adapt their protein production to survive. The translational machinery can be recruited by malignant cells to synthesize proteins required to promote their survival, even in times of high physiological and pathological stress. This phenomenon has been described in several cancers including in gliomas. Abnormal regulation of translation has encouraged the development of new therapeutics targeting the protein synthesis pathway. This approach could be meaningful for glioma given the fact that the median survival following diagnosis of the highest grade of glioma remains short despite current therapy. The identification of new targets for the development of novel therapeutics is therefore needed in order to improve this devastating overall survival rate. This review discusses current literature on translation in gliomas with a focus on the initiation step covering both the cap-dependent and cap-independent modes of initiation. The different translation initiation protagonists will be described in normal conditions and then in gliomas. In addition, their gene expression in gliomas will systematically be examined using two freely available datasets. Finally, we will discuss different pathways regulating translation initiation and current drugs targeting the translational machinery and their potential for the treatment of gliomas.
癌细胞不断暴露于环境应激源中，迫使它们适应蛋白质生产以存活。翻译机制可以被恶性细胞招募，以合成促进其存活所需的蛋白质，即使在生理和病理压力高的情况下也是如此。这种现象在包括神经胶质瘤在内的几种癌症中都有描述。翻译的异常调节鼓励了针对蛋白质合成途径的新治疗方法的发展。鉴于目前的治疗方法，即使在诊断出最高级别神经胶质瘤后，中位生存时间仍然很短，这种方法对于神经胶质瘤来说可能具有重要意义。因此，需要确定新的靶点来开发新的治疗方法，以提高这种毁灭性的总生存率。这篇综述讨论了胶质瘤中翻译的当前文献，重点介绍了涵盖帽依赖性和帽非依赖性起始的起始步骤。将在正常条件下和在神经胶质瘤中描述不同的翻译起始主角。此外，将使用两个免费提供的数据集系统地检查它们在神经胶质瘤中的基因表达。最后，我们将讨论调节翻译起始的不同途径以及针对翻译机制的当前药物及其治疗神经胶质瘤的潜力。
