Eukaryotic initiation factor 5A2 and human digestive system neoplasms

Abstract

Eukaryotic initiation factor 5A2 (eIF5A2), as one of the two isoforms in the family, is reported to be a novel oncogenic protein that is involved in multiple aspects of many types of human cancer. Overexpression or gene amplification of EIF5A2 has been demonstrated in many cancers. Accumulated evidence shows that eIF5A2 initiates tumor formation, enhances cancer cell growth, increases cancer cell metastasis, and promotes treatment resistance through multiple means, including inducing epithelial-mesenchymal transition, cytoskeletal rearrangement, angiogenesis, and metabolic reprogramming. Expression of eIF5A2 in cancer correlates with poor survival, advanced disease stage, as well as metastasis, suggesting that eIF5A2 function is crucial for tumor development and maintenance but not for normal tissue homeostasis. All these studies suggest that eIF5A2 is a useful biomarker in the prediction of cancer prognosis and serves as an anticancer molecular target. This review focuses on the expression, subcellular localization, post-translational modifications, and regulatory networks of eIF5A2, as well as its biochemical functions and evolving clinical applications in cancer, especially in human digestive system neoplasms.

Keywords: Acetylation modification; Cancer therapeutics; Drug resistance; Eukaryotic translation initiation factor 5A2; Hypusine modification.

Figure 1

unctions and subsequent pathways of eukaryotic initiation factor 5A2 in human digestive system neoplasms. Overexpression of Eukaryotic initiation factor 5A2 (eIF5A2) induces epithelial–mesenchymal transition (EMT) by enhancing RhoA/Rac1-GTPase and ITP60 GNC5-MTA1 activity in hepatocellular carcinoma (HCC). Overexpression of EIF5A2 also promotes colorectal carcinoma and gastric cancer cell aggressiveness by upregulating the C-myc/MTA axis to induce EMT. Increased expression of eIF5A2 contributes to angiogenesis in esophageal squamous cell carcinoma via the P38 MAPK/MMP2 pathway. eIF5A2 promotes cell proliferation and triggers cellular metabolic reprogramming in HCC cells, including glucose metabolism and fatty acid biosynthesis via upregulation of FASN and ACSS2. In HCC, eIF5A2 stimulates rearrangement of the cytoskeleton through activation of the RhoA/Rac1 GTPase signaling pathway. eIF5A2: Eukaryotic initiation factor 5A2; EMT: Epithelial–mesenchymal transition.