Role of NEK2A in human cancer and its therapeutic potentials.

Jiliang Xia,Zhimin Gu,Fenghuang Zhan,Reinaldo Franqui Machin

doi:10.1155/2015/862461

Abstract

Chromosome instability (CIN) has been identified as a common feature of most human cancers. A number of centrosomal kinases are thought to cause CIN in cancer cells. Part of those centrosomal kinases exhibit elevated expression in a wide variety of tumours and cancer cell lines. Additionally, critical roles in many aspects of cancer cell growth, proliferation, metastasis, and drug resistance have been assigned to some of these centrosomal kinases, such as polo-like kinase 1 (PLk1) and Aurora-A kinase. Recent studies from our group and others revealed that a centrosomal kinase, Never in Mitosis (NIMA) Related Kinase 2A (NEK2A), is frequently upregulated in multiple types of human cancers. Uncontrolled activity of NEK2A activates several oncogenic pathways and ABC transporters, thereby leading to CIN, cancer cell proliferation, metastasis, and enhanced drug resistance. In this paper, we highlight recent findings on the aberrant expression and functional significance of NEK2A in human cancers and emphasize their significance for therapeutic potentials.

Highlights

Cancer cells tend to show some degree of genetic instability
Chromosome instability (CIN) generates a disparity in chromosome number and an enhanced rate of loss of heterozygosity, which is frequently seen in cancer cells [3,4,5]
Never in Mitosis Related Kinase 2A APC/C (NEK2A) contributes to several biological processes of the tumor cell, including proliferation, metastasis, and drug resistance

Summary

Introduction

Cancer cells tend to show some degree of genetic instability. It is clear that high genetic change or instability plays a major role in cancer development [1]. Theodor Boveri observed abnormal chromosome quantities in cancer cells as early as a century ago [6] It was only in the recent years that CIN has been positively correlated with tumorigenesis, cancer progression, and therapeutic resistance [3,4,5]. Uncontrolled activity of centrosomal kinases can lead to spindle abnormalities, centrosome fragmentation, premature centriole splitting, multiple nucleuses, supernumerary centrosomes, and chromosome segregation errors. All those abnormal phenotype are important risk factors for CIN, indicating that overexpression of centrosomal kinases might drive tumor progression by promoting CIN [10, 11]. In view of previous studies, we speculated that NEK2A may be a novel potential biomarker for diagnosis and a possible therapeutic target for human cancers

Basic Biology of NEK2A and Validated

Aberrant Expression of NEK2A in Human Cancers

Therapeutic Potential of NEK2A

Findings

Conclusion