Forkhead box M1 transcription factor: a novel target for pulmonary arterial hypertension therapy
Forkhead box M1 (FoxM1), a member of forkhead family, plays a key role in carcinogenesis, progression, invasion, metastasis and drug resistance. Based on the similarities between cancer and pulmonary arterial hypertension, studies on the roles and mechanisms of FoxM1 in pulmonary arterial hypertension have been increasing. This article aims to review recent advances in the mechanisms of signal transduction associated with FoxM1 in pulmonary arterial hypertension.
Articles were retrieved from PubMed and MEDLINE published after 1990, including—but not limited to—FoxM1 and pulmonary arterial hypertension.
FoxM1 is overexpressed in pulmonary artery smooth muscle cells in both pulmonary arterial hypertension patients and animal models, and promotes pulmonary artery smooth muscle cell proliferation and inhibits cell apoptosis via regulating cell cycle progression. Multiple signaling molecules and pathways, including hypoxia-inducible factors, transforming growth factor-β/Smad, SET domain-containing 3/vascular endothelial growth factor, survivin, cell cycle regulatory genes and DNA damage response network, are reported to cross talk with FoxM1 in pulmonary arterial hypertension. Proteasome inhibitors are effective in the prevention and treatment of pulmonary arterial hypertension by inhibiting the expression and transcriptional activity of FoxM1.
FoxM1 has a crucial role in the pathogenesis of pulmonary arterial hypertension and may represent a novel therapeutic target. But more details of interaction between FoxM1 and other signaling pathways need to be clarified in the future.
KeywordsForkhead box M1 Proteasome inhibitor Pulmonary arterial hypertension Signaling pathway
We thank Prof. Ling Gu for insightful discussions and for the critical reading of this manuscript, and Dr. Xia Guo for language help.
LG contributed to literature review and drafting. HML contributed to concept and design, and critical revision. Both authors approved the final version of the manuscript.
No external funding was secured for this paper.
Compliance with ethical standards
Conflict of interest
The authors have no conflict of interest.
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