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.
驱动蛋白家族成员4A（KIF4A）属于驱动蛋白相关蛋白的驱动蛋白4亚家族，参与调控有丝分裂细胞分裂过程中染色体的凝集与分离。研究发现，KIF4A在肺癌、乳腺癌、结肠癌等多种癌症中的表达与患者不良预后相关，但其促进肿瘤发生的具体机制尚未明确。在骨肉瘤中，KIF4A的表达与癌症干细胞（CSCs）相关；而在乳腺癌中，其虽不参与维持CSCs，却能调控细胞迁移能力。基于此，我们在肺癌和胶质瘤中发现了影响癌症恶性程度的表型现象，并探究了其促进肿瘤发生的机制。结果表明，KIF4A能够影响肺癌干细胞（LCSCs）和胶质瘤干细胞（GSCs），并调控CSCs信号传导机制。此外，KIF4A通过调控上皮-间质转化（EMT）标志蛋白的表达来调节细胞迁移能力。KIF4A还调控分泌因子纤溶酶原激活物抑制剂-1（PAI-1）的表达，证明其通过自分泌环路维持癌症恶性表型。综上所述，这些发现表明KIF4A通过调控与癌症复发和转移相关的CSCs及EMT过程，在肺癌和胶质瘤中具有作为新型治疗靶点与预后标志物的潜在价值。
Impact of KIF4A on Cancer Stem Cells and EMT in Lung Cancer and Glioma
肿瘤(癌症)患者之家