Mitotic protein kinase-driven crosstalk of machineries for mitosis and metastasis

Abstract

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.

Cancer: Linking cell division to cancer spread

Improving understanding of the mechanisms linking cell division and cancer spread (metastasis) could provide novel strategies for treatment. A group of enzymes involved in cell division (mitosis) are also thought to play critical roles in the spread of cancers. Hyungshin Yim at Hanyang University in Ansan, South Korea, and co-workers in Korea and the USA reviewed the roles of several mitotic enzymes that are connected with metastasis as well as tumorigenesis. They discussed how these enzymes modify cytoskeletal proteins and other substrates during cancer progression. Some regulatory control of cell cytoskeletal structures is required for cancer cells to metastasize. Recent research has uncovered crosstalk between mitotic enzymes and metastatic cytoskeletal molecules in various cancers. Targeting mitotic enzymes and the ways they influence cytoskeletal mechanisms could provide valuable therapeutic strategies for suppressing metastasis.