Department of Pharmacy, College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Gyeonggi-do, 15588, Korea.
Department of Biological and Health Sciences, Texas A&M University-Kingsville, Kingsville, TX, 78363, USA.
Exp Mol Med. 2022 Apr;54(4):414-425. doi: 10.1038/s12276-022-00750-y. Epub 2022 Apr 4.
Accumulating evidence indicates that mitotic protein kinases are involved in metastatic migration as well as tumorigenesis. Protein kinases and cytoskeletal proteins play a role in the efficient release of metastatic cells from a tumor mass in the tumor microenvironment, in addition to playing roles in mitosis. Mitotic protein kinases, including Polo-like kinase 1 (PLK1) and Aurora kinases, have been shown to be involved in metastasis in addition to cell proliferation and tumorigenesis, depending on the phosphorylation status and cellular context. Although the genetic programs underlying mitosis and metastasis are different, the same protein kinases and cytoskeletal proteins can participate in both mitosis and cell migration/invasion, resulting in migratory tumors. Cytoskeletal remodeling supports several cellular events, including cell division, movement, and migration. Thus, understanding the contributions of cytoskeletal proteins to the processes of cell division and metastatic motility is crucial for developing efficient therapeutic tools to treat cancer metastases. Here, we identify mitotic kinases that function in cancer metastasis as well as tumorigenesis. Several mitotic kinases, namely, PLK1, Aurora kinases, Rho-associated protein kinase 1, and integrin-linked kinase, are considered in this review, as an understanding of the shared machineries between mitosis and metastasis could be helpful for developing new strategies to treat cancer.
越来越多的证据表明，有丝分裂蛋白激酶参与转移以及肿瘤发生。蛋白激酶和细胞骨架蛋白在肿瘤微环境中，除了在有丝分裂中发挥作用外，还在肿瘤细胞从肿瘤块中有效释放中发挥作用。有丝分裂蛋白激酶，包括 Polo 样激酶 1（PLK1）和 Aurora 激酶，除了参与细胞增殖和肿瘤发生外，还被证明参与转移，这取决于磷酸化状态和细胞环境。尽管有丝分裂和转移的遗传程序不同，但相同的蛋白激酶和细胞骨架蛋白可以参与有丝分裂和细胞迁移/侵袭，导致迁移性肿瘤。细胞骨架重塑支持包括细胞分裂、运动和迁移在内的多种细胞事件。因此，了解细胞骨架蛋白对细胞分裂和转移运动过程的贡献对于开发治疗癌症转移的有效治疗工具至关重要。在这里，我们确定了在癌症转移和肿瘤发生中起作用的有丝分裂激酶。在本综述中考虑了几种有丝分裂激酶，即 PLK1、Aurora 激酶、Rho 相关蛋白激酶 1 和整合素连接激酶，因为对有丝分裂和转移之间共享机制的理解可能有助于开发治疗癌症的新策略。
