Kinesin family member 2A promotes cancer cell viability, mobility, stemness, and chemoresistance to cisplatin by activating the PI3K/AKT/VEGF signaling pathway in non-small cell lung cancer.

Kinesin family member 2A (KIF2A), a member of the kinesin-13 protein family that functions as a regulator in mitosis, neuron branch extension, etc., is reported to be involved in the pathogenesis of multiple cancers. This study assessed KIF2A effects on cancer cell functions and sensitivity to chemotherapy and its interaction with PI3K/AKT/VEGF signaling when mediating cancer cell functions, and chemosensitivity in non-small cell lung cancer (NSCLC). Human bronchial epithelial cell line BEAS-2B and human NSCLC cell lines NCI-H1299, NCI-H385, NCI-H1650, and A549 were used. The KIF2A and negative control (NC) overexpression plasmids were transfected into A549 cells; KIF2A and NC knock-down plasmids were transfected into NCI-H1299 cells. Rescue experiments were conducted by transfecting PI3K and NC knock-down plasmids into KIF2A overexpression A549 cells and transfecting PI3K and NC overexpression plasmids into KIF2A knock-down NCI-H1299 cells. Proliferation, apoptosis, migration, invasion, CD133 proportion, sensitivity to chemotherapeutics, and PI3K/AKT/VEGF pathway were assessed. KIF2A mRNA and protein expression levels were elevated in NCI-H1299, NCI-H385, NCI-H1650, and A549 cells compared to BEAS-2B cells. KIF2A overexpression elevated proliferation, migration, invasion, stemness, and resistance to cisplatin but did not affect apoptosis or resistance to pemetrexed in A549 cells. Furthermore, KIF2A knock-down repressed proliferation, migration, invasion, stemness, and resistance to cisplatin, but not to pemetrexed, and it enhanced apoptosis in NCI-H1299 cells. Rescue experiments showed that the PI3K/AKT/VEGF pathway compensated for KIF2A effects on cell functions and sensitivity to cisplatin in A549 and NCI-H1299 cells. In conclusion, KIF2A advocates NSCLC cell viability, mobility, stemness, and chemoresistance to cisplatin by activating the PI3K/AKT/VEGF signaling pathway.