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Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jun 15, 2019; 11(6): 449-458
Published online Jun 15, 2019. doi: 10.4251/wjgo.v11.i6.449
Eukaryotic initiation factor 5A2 and human digestive system neoplasms
Qing-Bin Meng, Jing-Jing Peng, Zi-Wei Qu, Xiao-Min Zhu, Zhang Wen, Wei-Ming Kang
Qing-Bin Meng, Zi-Wei Qu, Department of Gastrointestinal Surgery, the First Hospital of Wuhan City, Wuhan 430022, Hubei Province, China
Jing-Jing Peng, Department of Gastroenterology, General Hospital of the Yangtze River Shipping, Wuhan 430015, Hubei Province, China
Zhang Wen, Department of Hepato-Biliary-Pancreatic Surgery and Liver Transplantation, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Wei-Ming Kang, Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Author contributions: All authors equally contributed to conception and design of the study, literature review and analysis, drafting, critical revision and editing of the manuscript, and final approval of the submitted version.
Supported by Natural Science Foundation of Hubei Province, No. 2016CFB596; Wuhan City Medical Research Project, Nos. WX15B14 and WX17Q39; and Hubei Province Scientific Research Project, No. WJ2015MB137.
Conflict-of-interest statement: There are no potential conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Wei-Ming Kang, MD, Professor, Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuai Fu Yuan, Dongcheng District, Beijing 100730, China. kangweiming@163.com
Telephone: +86-10-69152213 Fax: +86-10-69152213
Received: January 2, 2019
Peer-review started: January 4, 2019
First decision: March 14, 2019
Revised: April 17, 2019
Accepted: May 3, 2019
Article in press: May 4, 2019
Published online: June 15, 2019
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: Eukaryotic translation initiation factor 5A2, Hypusine modification, Acetylation modification, Drug resistance, Cancer therapeutics

Core tip: Eukaryotic initiation factor 5A2 (eIF5A2) is one of only two cellular proteins that contain the unusual amino acid hypusine. eIF5A2 initiates tumor formation, enhances cancer cell growth, increases metastasis, and promotes treatment resistance through inducing epithelial–mesenchymal transition, cytoskeletal rearrangement, angiogenesis, and metabolic reprogramming. Isoform eIF5A2 represents a promising target for treatment of human digestive system cancer. Our objective was to consolidate the current literature to better understand the expression, subcellular localization, post-translational modifications, and regulatory networks of eIF5A2, as well as its biochemical functions and evolving clinical applications in human digestive system cancer.