Homeodomain interacting protein kinase-2 phosphorylates FOXM1 and promotes FOXM1-mediated tumor growth in renal cell carcinoma.

Forkhead Box M1 (FOXM1) is a member of the forkhead/winged-helix transcription factors regulating proliferation-associated genes and is critical to DNA replication and mitosis. With this said, the function of FOXM1 in renal cell carcinoma (RCC) has not been clearly elucidated. Thus, in this study, the expression pattern of FOXM1 was significantly upregulated in RCC tissues compared with adjacent noncancerous tissues. Moreover, using liquid chromatography with tandem mass spectrometry (LC-MS/MS), FOXM1 can interact with homeodomain interacting protein kinase-2 (HIPK2). In addition, FOXM1 can be phosphorylated by HIPK2. Furthermore, HIPK2 knockdown inhibits FOXM1 phosphorylation and reduces transcription of FOXM1 associated genes: Cyclin B1 and Aurora B. In addition, HIPK2 knockdown hampers the RCC cells cycle progression and suppresses cell viability in vivo and in vitro. In conclusion, the phosphorylation of FOXM1 by HIPK2 can promote FOXM1 transcription activity and cell proliferation in RCC, thus, indicating a potential mechanism for the treatment of human RCC in the future.