Human Elongation Factor 4 Regulates Cancer Bioenergetics by Acting as a Mitochondrial Translation Switch.
Ping ZhuYongzhang LiuFenglin ZhangXiufeng BaiZilei ChenFugen ShangguanBo ZhangLingyun ZhangQianqian ChenDeyao XieLinhua LanXiangdong XueXing-Jie LiangBin LuTaotao WeiYan QinPublished in: Cancer research (2018)
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.
Keyphrases
- oxidative stress
- endothelial cells
- papillary thyroid
- poor prognosis
- cell death
- squamous cell
- quality control
- induced pluripotent stem cells
- diabetic rats
- gene expression
- pluripotent stem cells
- childhood cancer
- signaling pathway
- long non coding rna
- lymph node metastasis
- squamous cell carcinoma
- young adults
- genome wide
- single cell
- dna methylation
- cell cycle arrest
- transcription factor
- respiratory tract
- pi k akt