Inhibition of KIF22 suppresses cancer cell proliferation by delaying mitotic exit through upregulating CDC25C expression.

ABSTRACT

KIF22 is a microtubule-dependent molecular motor protein with DNA-binding capacity. It is well known that KIF22 plays a critical role in cell mitosis as a motor protein; however, the role of altered KIF22 expression and its transcriptional regulatory function in cancer development have not yet been defined. This study showed that KIF22 was overexpressed in human cancer tissues, and inhibition of KIF22 significantly led to accumulation of cells in the G2/M phases, resulting in suppression of cancer cell proliferation. The investigation of the molecular mechanisms demonstrated that cell division cycle 25C (CDC25C) is a direct transcriptional target of KIF22, and inhibition of KIF22 increased CDC25C expression and cyclin-dependent kinase 1 (CDK1) activity, resulting in delayed mitotic exit. Phosphorylation of KIF22 was required for its transcriptional regulatory function and the reduction of CDK1 activity. Thus, we conclude that inhibition of KIF22 suppresses cancer cell proliferation by delaying mitotic exit through the transcriptional upregulation of CDC25C.