FOXM1 (Forkhead box M1) in tumorigenesis: overexpression in human cancer, implication in tumorigenesis, oncogenic functions, tumor-suppressive properties, and target of anticancer therapy.

FOXM1 (Forkhead box M1) is a typical proliferation-associated transcription factor and is also intimately involved in tumorigenesis. FOXM1 stimulates cell proliferation and cell cycle progression by promoting the entry into S-phase and M-phase. Additionally, FOXM1 is required for proper execution of mitosis. In accordance with its role in stimulation of cell proliferation, FOXM1 exhibits a proliferation-specific expression pattern and its expression is regulated by proliferation and anti-proliferation signals as well as by proto-oncoproteins and tumor suppressors. Since these factors are often mutated, overexpressed, or lost in human cancer, the normal control of the foxm1 expression by them provides the basis for deregulated FOXM1 expression in tumors. Accordingly, FOXM1 is overexpressed in many types of human cancer. FOXM1 is intimately involved in tumorigenesis, because it contributes to oncogenic transformation and participates in tumor initiation, growth, and progression, including positive effects on angiogenesis, migration, invasion, epithelial-mesenchymal transition, metastasis, recruitment of tumor-associated macrophages, tumor-associated lung inflammation, self-renewal capacity of cancer cells, prevention of premature cellular senescence, and chemotherapeutic drug resistance. However, in the context of urethane-induced lung tumorigenesis, FOXM1 has an unexpected tumor suppressor role in endothelial cells because it limits pulmonary inflammation and canonical Wnt signaling in epithelial lung cells, thereby restricting carcinogenesis. Accordingly, FOXM1 plays a role in homologous recombination repair of DNA double-strand breaks and maintenance of genomic stability, that is, prevention of polyploidy and aneuploidy. The implication of FOXM1 in tumorigenesis makes it an attractive target for anticancer therapy, and several antitumor drugs have been reported to decrease FOXM1 expression.