Forkhead box protein M1 (FOXM1) (FOXM1)

Forkhead box protein M1 (FOXM1) is a critical transcription factor and a member of the Forkhead box family that serves as a master regulator of the cell cycle, specifically governing the transition from G1 to S phase and G2 to M phase (UniProt P00338). It coordinates the expression of a cluster of genes essential for DNA replication, mitosis, and genomic stability, including Aurora B kinase and Cyclin B1 (PubMed: 28233475). In the context of human pathology, FOXM1 is recognized as a potent proto-oncogene that is overexpressed in nearly all human cancers, where it promotes tumor proliferation, epithelial-mesenchymal transition (EMT), metastasis, and resistance to chemotherapy (NCBI Gene ID: 2305; PubMed: 30106342). Beyond oncology, the FOXM1 axis is involved in tissue repair and fibrosis, particularly in the lungs and liver (PubMed: 25616106). Therapeutic targeting of FOXM1 has historically been challenging due to its nature as a transcription factor, but current strategies include small molecule inhibitors like FDI-6 that block DNA binding and thiazole antibiotics such as thiostrepton that trigger its degradation (PubMed: 24671021). Its role as a central node in oncogenic signaling makes it a high-priority target for developing next-generation precision medicines.

Other names

Forkhead box M1HFH-11MPP2TridentWINFKHL16INS-1HNF-3Forkhead-related protein FKHL16

FOXM1 inhibitors function by disrupting the protein's ability to bind to its target DNA sequences, suppressing its transcriptional activity, or by promoting its proteasomal degradation (PubMed: 24671021, 28233475). Some agents, like thiazole antibiotics, specifically target the FOXM1-DNA interaction or reduce FOXM1 mRNA and protein levels (PubMed: 21169497).