Oncogenic activation of EEF1A2 expression: a journey from a putative to an established oncogene

Abstract

Abstract Protein synthesis via translation is a central process involving several essential proteins called translation factors. Although traditionally described as cellular “housekeepers,” multiple studies have now supported that protein initiation and elongation factors regulate cell growth, apoptosis, and tumorigenesis. One such translation factor is eukaryotic elongation factor 1 alpha 2 (EEF1A2), a member of the eukaryotic elongation factor family, which has a canonical role in the delivery of aminoacyl-tRNA to the A-site of the ribosome in a guanosine 5′-triphosphate (GTP)-dependent manner. EEF1A2 differs from its closely related isoform, EEF1A1, in tissue distribution. While EEF1A1 is present ubiquitously, EEF1A2 replaces it in specialized tissues. The reason why certain specialized tissues need to essentially switch EEF1A1 expression altogether with EEF1A2 remains to be answered. Abnormal “switch on” of the EEF1A2 gene in normal tissues is witnessed and is seen as a cause of oncogenic transformation in a wide variety of solid tumors. This review presents the journey of finding increased expression of EEF1A2 in multiple cancers, establishing molecular mechanism, and exploring it as a target for cancer therapy. More precisely, we have compiled studies in seven types of cancers that have reported EEF1A2 overexpression. We have discussed the effect of aberrant EEF1A2 expression on the oncogenic properties of cells, signaling pathways, and interacting partners of EEF1A2. More importantly, in the last part, we have discussed the unique potential of EEF1A2 as a therapeutic target. This review article gives an up-to-date account of EEF1A2 as an oncogene and can draw the attention of the scientific community, attracting more research.

Keywords

• Cancer
• EEF1A1
• EEF1A2
• PI3K
• AKT