Tang Bu-Fu, Yan Ruo-Chen, Wang Si-Wei, Zeng Zhao-Chong, Du Shi-Suo
Department of Radiation Oncology, Fudan University Zhongshan Hospital, Fenglin Road 188, 200030, Shanghai, China.
School of Medicine, Zhejiang University, Hangzhou, China.
Cancer Lett. 2023 Apr 28;560:216126. doi: 10.1016/j.canlet.2023.216126. Epub 2023 Mar 16.
Maternal embryonic leucine zipper kinase (MELK) is a member of the AMPK (AMP-activated protein kinase) protein family, which is widely and highly expressed in multiple cancer types. Through direct and indirect interactions with other targets, it mediates various cascades of signal transduction processes and plays an important role in regulating tumor cell survival, growth, invasion and migration and other biological functions. Interestingly, MELK also plays an important role in the regulation of the tumor microenvironment, which can not only predict the responsiveness of immunotherapy, but also affect the function of immune cells to regulate tumor progression. In addition, more and more small molecule inhibitors have been developed for the target of MELK, which exert important anti-tumor effects and have achieved excellent results in a number of clinical trials. In this review, we outline the structural features, molecular biological functions, potential regulatory mechanisms and important roles of MELK in tumors and tumor microenvironment, as well as substances targeting MELK. Although many molecular mechanisms of MELK in the process of tumor regulation are still unknown, it is worth affirming that MELK is a potential tumor molecular therapeutic target, and its unique superiority and important role provide clues and confidence for subsequent basic research and scientific transformation.
母体胚胎亮氨酸拉链激酶(MELK)是AMPK(AMP激活的蛋白激酶)蛋白家族的成员,在多种癌症类型中广泛且高度表达。通过与其他靶点的直接和间接相互作用,它介导各种信号转导过程级联反应,并在调节肿瘤细胞存活、生长、侵袭和迁移等生物学功能中发挥重要作用。有趣的是,MELK在肿瘤微环境的调节中也发挥着重要作用,它不仅可以预测免疫治疗的反应性,还能影响免疫细胞的功能以调节肿瘤进展。此外,针对MELK靶点已开发出越来越多的小分子抑制剂,它们发挥着重要的抗肿瘤作用,并在多项临床试验中取得了优异的成果。在这篇综述中,我们概述了MELK在肿瘤和肿瘤微环境中的结构特征、分子生物学功能、潜在调节机制及重要作用,以及靶向MELK的物质。尽管MELK在肿瘤调节过程中的许多分子机制仍不清楚,但值得肯定的是,MELK是一个潜在的肿瘤分子治疗靶点,其独特的优势和重要作用为后续的基础研究和科学转化提供了线索和信心。