Institute of Pharmacy, Nirma University, Ahmedabad, India.
Fundam Clin Pharmacol. 2022 Oct;36(5):766-776. doi: 10.1111/fcp.12777. Epub 2022 Apr 2.
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.
男性和女性中第二常见的癌症是肺癌。化疗耐药性是与肺癌治疗相关的主要问题。放射治疗和手术也会导致肺癌患者复发;这表明需要开发针对新靶点的新型药物。有丝分裂期不可进入(NIMA)相关激酶 2(NEK2)是一种丝氨酸/苏氨酸激酶,与 NIMA 相关激酶(NEK)家族有关。NEK2 在调节有丝分裂过程中发挥着重要作用,如中心体复制和分离、动粒附着、纺锤体组装检查点和微管稳定。几项体外、体内和临床研究证实,NEK2 在包括肺癌在内的各种类型的癌症中过度表达。非小细胞肺癌(NSCLC)细胞中 NEK2 的过度表达增加了细胞增殖和染色体不稳定性。NEK2 的过度表达导致其下游蛋白如β-连环蛋白、MAD2、Hec1、根蛋白、C-Nap1、CDC20、Cep68 和 Sgo1 的激活。Akt、β-连环蛋白和 Wnt 通路的激活可以促进肺癌细胞的生长和转移。这种证实表明,NEK2 是治疗包括肺癌在内的许多癌症的新靶点。本综述提供了关于 NEK2 的功能和调节的想法,并通过讨论与 NEK2 相关的体外、体内和临床研究,强调了 NEK2 在肺癌中的作用。