Impact of KIF4A on Cancer Stem Cells and EMT in Lung Cancer and Glioma

Simple Summary Kinesin family member 4A (KIF4A) is associated with poor prognosis in lung cancer and glioma. Our research found that KIF4A affects cancer stem cells (CSCs) and promotes epithelial-to-mesenchymal transition (EMT), a process linked to cancer's aggressiveness and spread. We also identified its influence on the secretion of plasminogen activator inhibitor-1 (PAI-1), a key factor in cancer malignancy. KIF4A appears to sustain malignancy through an autocrine loop with PAI-1. These findings suggest that KIF4A has the potential to serve as a novel therapeutic target and prognostic marker in lung cancer and glioma, shedding light on mechanisms involved in cancer recurrence and metastasis.Abstract Kinesin family member 4A (KIF4A) belongs to the kinesin 4 subfamily of kinesin-related proteins and is involved in the regulation of chromosome condensation and segregation during mitotic cell division. The expression of KIF4A in various types of cancer, including lung, breast, and colon cancer, has been found to be associated with poor prognosis in cancer patients. However, the exact mechanism by which it promotes tumorigenesis is not yet understood. In osteosarcoma, the expression of KIF4A has been shown to be associated with cancer stem cells (CSCs), whereas in breast cancer, it is not associated with the maintenance of CSCs but regulates the migratory ability of cells. In this light, we identified phenotypic phenomena affecting the malignancy of cancer in lung cancer and glioma, and investigated the mechanisms promoting tumorigenesis. As a result, we demonstrated that KIF4A affected lung cancer stem cells (LCSCs) and glioma stem cells (GSCs) and regulated CSC signaling mechanisms. In addition, the migratory ability of cells was regulated by KIF4A, and epithelial-to-mesenchymal transition (EMT) marker proteins were controlled. KIF4A regulated the expression of the secretory factor plasminogen activator inhibitor-1 (PAI-1), demonstrating that it sustains cancer malignancy through an autocrine loop. Taken together, these findings suggest that KIF4A regulates CSCs and EMT, which are involved in cancer recurrence and metastasis, indicating its potential value as a novel therapeutic target and prognostic marker in lung cancer and glioma.