FOXM1 (Forkhead box M1) in Tumorigenesis

Abstract

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.

Overexpression of FOXM1 predicts poor prognosis and promotes cancer cell proliferation, migration and invasion in epithelial ovarian cancer

“…Similarly, we found that depletion of FOXM1 by transfection with FOXM1 shRNA could suppress cell growth, invasion and metastasis. Several studies have shown that FOXM1 could promote cell growth, invasion and metastasis in various cell types [4,5,24,25]. Here, we reached the same conclusion in EOC.…”

Large-Scale Label-Free Comparative Proteomics Analysis of Polo-Like Kinase 1 Inhibition via the Small-Molecule Inhibitor BI 6727 (Volasertib) in BRAFV600E Mutant Melanoma Cells

“…55 Plk1 is involved in a positive feedback loop with FoxM1, where Plk1-dependent phosphorylation is required for efficient FoxM1 activation, which in turn is required for expression of multiple mitotic regulators, including Plk1. 52 Interestingly, proteasome inhibitors have been shown to suppress FoxM1 transcriptional activity, suggesting that proteasome-dependent degradation may confer a level of indirect regulation to Plk1 overexpression in human carcinomas.…”

Maternal Embryonic Leucine Zipper Kinase: Key Kinase for Stem Cell Phenotype in Glioma and Other Cancers

“…Aurora A/B, Survivin, and CDC25B)(22, 23). FOXM1 is also required for a variety of cancer cell phenotypes including cell proliferation, mitotic progression, DNA damage repair, angiogenesis, and suppression of apoptosis(24–27). Siomycin A treatment significantly decreased the proportions of FOXM1(+), MELK(+) cells in GBM tumorspheres in a dose dependent manner, suggesting that siomycin A may abrogate cancer-specific MELK signaling through disruption of MELK-driven FOXM1 transcriptional activity.…”