Human Elongation Factor 4 Regulates Cancer Bioenergetics by Acting as a Mitochondrial Translation Switch.
Human Elongation Factor 4 Regulates Cancer Bioenergetics by Acting as a Mitochondrial Translation Switch.
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人类伸长因子 4 通过充当线粒体翻译开关来调节癌症生物能量。
DOI：
10.1158/0008-5472.can-17-2059
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发表时间：
2018
期刊：
影响因子：
11.2
通讯作者：
Qin Yan
中科院分区：
文献类型：
--
作者：
Zhu Ping;Liu Yongzhang;Zhang Fenglin;Bai Xiufeng;Chen Zilei;Shangguan Fugen;Zhang Bo;Zhang Lingyun;Chen Qianqian;Xie Deyao;Lan Linhua;Xue Xiangdong;Liang Xing Jie;Lu Bin;Wei Taotao;Qin Yan
线粒体调节细胞生物能量学和氧化还原状态，并影响肿瘤发生所需的多种信号通路。在这项研究中，我们确定线粒体翻译延长因子4（EF4）是肿瘤进展的关键组成部分。EF 4在人体组织中普遍存在，定位于线粒体（mtEF 4），并对呼吸链生物合成进行质量控制。mtEF4基因敲除可诱导呼吸链复合体缺陷和细胞凋亡，而其过表达则可刺激肿瘤的发生。在多种癌症中，患者肿瘤组织中mtEF4的表达增加。这些发现表明，mtEF4的表达可能会促进肿瘤的发生，通过不平衡的调节线粒体的活动和随后的变化的细胞氧化还原。因此，失调的线粒体翻译可能在多种人类癌症的病因学和发展中起着至关重要的作用。©2018 AACR.
Mitochondria regulate cellular bioenergetics and redox states and influence multiple signaling pathways required for tumorigenesis. In this study, we determined that the mitochondrial translation elongation factor 4 (EF4) is a critical component of tumor progression. EF4 was ubiquitous in human tissues with localization to the mitochondria (mtEF4) and performed quality control on respiratory chain biogenesis. Knockout of mtEF4 induced respiratory chain complex defects and apoptosis, while its overexpression stimulated cancer development. In multiple cancers, expression of mtEF4 was increased in patient tumor tissues. These findings reveal that mtEF4 expression may promote tumorigenesis via an imbalance in the regulation of mitochondrial activities and subsequent variation of cellular redox. Thus, dysregulated mitochondrial translation may play a vital role in the etiology and development of diverse human cancers.Significance:Dysregulated mitochondrial translation drives tumor development and progression.Cancer Res; 78(11); 2813–24. ©2018 AACR.