GENERAL COMMENTARY published: 06 June 2013 doi: 10.3389/fonc. 2013.00150 of FOXM1 ( Gartel, 2010, 2012). According to this model, siomycin A, thiostrepton, and other proteasome inhibitors hinder the proteasomal degradation of a negative regulator of FOXM1 (NRFM), which in return directly or indirectly inhibits the activity of FOXM1 as a transcription factor ( Gartel, 2011). Because FOXM1 is involved in a positive feedback loop and activates its own transcription ( Halasi and Gartel, 2009), inhibition of FOXM1 transcriptional activity leads to a decrease in its expression ( Gartel, 2010). This model also anticipates that all proteasome inhibitors regardless of their structure will inhibit FOXM1 transcriptional activity through stabilizing the NRFM and subsequently (via the auto-regulatory loop) inhibit FOXM1 expression ( Gartel, 2011, 2012). Overall, inhibition of FOXM1 transcriptional activity by siomycin A, thiostrepton, and other proteasome inhibitors is an essential part of their regulation of FOXM1.

FOXM1 is without a doubt emerging as a critical regulator of cancer development ( Halasi and Gartel, 2013) that may affect all hallmarks of cancer ( Hanahan and Weinberg, 2012). Originally, it was identified as a key regulator of cell proliferation and cell cycle progression; however, in the past few years FOXM1 became one of the central contributors to tumorigenesis. Growing body of evidence suggests that targeting this single transcription factor may have great promise for inhibiting tumor development. Great efforts are currently being undertaken to find more specific inhibitors of FOXM1 and to elucidate their mechanism of action. I believe it is essential for the scientific community to have correct information about the regulation of FOXM1 by FOXM1 inhibitors in order to progress and accelerate research in the FOXM1 field.