Role of NIMA‐related kinase 2 in lung cancer: Mechanisms and therapeutic prospects

Abstract

The second most common cancer in both males and females is lung cancer. Chemotherapeutic resistance is the main problem associated with the treatment of lung cancer. Radiation therapy and surgery also produce recurrence in lung cancer patients; this shows the need to develop novel agents acting on new targets. A never in mitosis (NIMA)-related kinase 2 (NEK2) is a serine/threonine kinase associated with the family of NIMA-related kinase (NEK). NEK2 plays an important role in the regulating mitotic processes, such as centrosome duplication and separation, kinetochore attachment, spindle assembly checkpoint, and microtubule stabilization. Several in vitro, in vivo, and clinical studies have confirmed the overexpression of NEK2 in various types of cancers including lung cancer. Overexpression of NEK2 in non-small cell lung cancer (NSCLC) cells increased cell proliferation and chromosomal instability. The overexpression of NEK2 results in the activation of its downstream proteins such as β-catenin, MAD2, Hec1, rootletin, C-Nap1, CDC20, Cep68, and Sgo1. Activation of the Akt, β-catenin, and Wnt pathways could promote growth and metastasis of lung cancer cells. Such confirmation suggests that NEK2 is a novel target for treating many cancers including lung cancer. The current review provides an idea about functions and regulation of NEK2 and emphasizes about the role of NEK2 in lung cancer by discussing in vitro, in vivo, and clinical studies pertaining to the same.

NEK2 promotes TP53 ubiquitination to enhance the proliferation and migration of TP53 wild-type glioblastoma cells

“…The NIMA-related kinase (NEK) 2, a serine/threonine kinase belonging to the NEK family, exhibits specific localization at the centrosome. It is widely acknowledged as a multifunctional protein involved in regulating various aspects of the cell cycle [6][7][8][9][10]. NEK2 as multiple research studies have consistently observed its increased expression in different types of cancers and its correlation with poor overall survival results [11][12][13][14].…”

“…The NIMA-related kinase (NEK) 2, a serine/threonine kinase belonging to the NEK family, exhibits specific localization at the centrosome [6]. NEK2 is widely acknowledged as a versatile protein involved in the regulation of various aspects of cell cycle, including replication and segregation of centrosomes, stabilization of microtubules, attachment of kinetochores, and activation of the spindle assembly checkpoint [7][8][9][10]. In the realm of scientific academia, there has been considerable focus on the significant involvement of NEK2 in the development of tumors in recent years.…”

Evaluating the Expression and Prognostic Value of Genes Encoding Microtubule-Associated Proteins in Lung Cancer

“…It is known that NEK2 plays an important role in stabilizing microtubules during mitotic processes. Elevated levels of NEK2 induce cell proliferation and chromosome instability in NSCLC cells [ 74 ]. We provided consistent evidence for the upregulation and prognostic value of NEK2 in LUAD and found that TP53 and PDGFRA mutations were correlated with its elevated expression.…”