KIF4A promotes genomic stability and progression of endometrial cancer through regulation of TPX2 protein degradation

Abstract Kinesin family member 4A (KIF4A) belongs to the kinesin superfamily proteins, which are closely associated with mitophagy. Nonetheless, the role of KIF4A in endometrial cancer (EC) remains poorly characterized. The present study showed that KIF4A not only was upregulated but also predicted poor prognosis in patients with EC. KIF4A knockdown in EC cells resulted in attenuated proliferative capacity in vitro and in vivo. Transcriptome sequencing and gene function analysis revealed that KIF4A contributed to the maintenance of EC cells' genomic stability and that KIF4A knockdown induced the DNA damage response, cell cycle arrest, and apoptosis. Mechanistically, KIF4A interacted with TPX2 (a protein involved in DNA damage repair to cope with the replication pressure) to enhance its stability via inhibition of TPX2 ubiquitination and eventually ensured the genomic stability of EC cells during mitosis. Taken together, our results indicated that KIF4A functions as a tumor oncogene that facilitates EC progression via the maintenance of genomic stability. Therefore, targeting the KIF4A/TPX2 axis may provide new concepts and strategies for the treatment of patients with EC.